Associations of CXCL1 gene 5’UTR variations with ovarian cancer

Associations of CXCL1 gene 5’UTR variations with ovarian cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Associations of CXCL1 gene 5’UTR variations with ovarian cancer Man Guo, Chao Xu, Yan-Zhe Chen, Qi-Wen Sun, Xin-Ying Zhao, Xin Liu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.18650/v4 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Apr, 2020 Read the published version in Journal of Ovarian Research → Version 4 posted 4 You are reading this latest preprint version Show more versions Abstract Background: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC. Methods: We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9). Results: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients. Conclusions: Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population. Cancer Biology Sexual & Reproductive Medicine Ovarian cancer Chronic inflammation Chemokines CXCL1 5’UTR Figures Figure 1 Introduction Globally, there are about 2.4 hundred thousand new ovarian cancer (OC) cases and about 1.5 hundred thousand deaths caused by this disease annually [ 1 ]. OC is the 7th most common and 5 th most lethal cancer among women worldwide [ 2 ]. The incidence rates of OC are highest in northern and eastern Europe, and lowest in Asia and Africa [ 1 ]. In the past decades, however, the morbidity has considerably decreased in many previously high incidence countries but, in contrast, is increasing in some low incidence countries, such as China [ 1 , 3 ]. The 5-years survival rates of OC range from 30.3% to 44.1%, depending on the specific subtypes and stages at the time of diagnosis or treatment [ 4 , 5 ]. Early detection and treatment of this disease can significantly increase the survival rate of OC, but, due to the lack of specific signs or symptoms at early stages, this disease is usually diagnosed only at late stages [ 6 ]. The recurrence rate of this disease is also very high, often leading to death of the patient, who might have achieved a clinical complete remission after primary therapy [ 5 , 6 ]. So far, several genetic and non-genetic factors have been found to be associated with OC. Women with affected first-degree relatives usually have higher risks for OC [ 7 ], and women, who have relatives diagnosed with OC below 50 years old, have even higher OC risks [ 8 ]. Many gene mutations have been associated with sporadic OC patients, including BRCA1 and 2 [ 9 ], BRIP1 [ 10 ] and RAD51 [ 11 ]. Oral contraceptive use and tubal ligation seem to be protective factors [ 12 , 13 ], whereas older menopausal ages, obesity, menopausal hormone therapy use, a history of endometriosis and smoking are all risk factors [ 14-16 ]. Chronic inflammation, such as those caused by asbestos or talc exposure, endometriosis or pelvic inflammatory diseases, has also been suggested to be a risk factor for OC [ 17 , 18 ]. On the other side, anti-inflammatory medications, e.g., acetaminophen and low-dose of aspirin are protective factors for OC [ 19 , 20 ]. Immunotherapies, including immune checkpoint blockade and cancer vaccines, also have many special roles in immune recognition and immune regulation of the OC cells [ 21 ]. Chemokines expressed in tumor or stromal cells may facilitate tumor angiogenesis and in the meantime suppress immune-mediated tumor elimination, and as a result are associated with cancers [ 22-24 ]. C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC subfamily of chemokines and an oncogenic factor in many cancers [ 25 , 26 ]. It can transactivate EGFR in OC through binding to the G-protein coupled receptor CXC receptor 2 (CXCR2) [ 27 ]. Abnormal expression of CXCL1 is associated with many tumors [ 28 ], but the associated haplotypes remained largely unknown. In this work, we investigated variants in the CXCL1 gene for their associations with the risk of OC in the Chinese Han population. We found that variant rs11547681 was associated with ovarian cancer and demonstrated the 5’UTR for the functions of CXCL1. Materials And Methods Study population A total of 300 sporadic OC cases and 400 normal controls (Table 1) were assembled for this study at the Department of Gynaecology and Obstetrics and Medical Examination Center of the Second Affiliated Hospital of Harbin Medical University, Harbin, China. From each participant, we obtained a written informed consent. This work has been reviewed and approved by the Ethics Committee of Harbin Medical University. We also confirmed that all experiments were performed in accordance with relevant guidelines and regulations and were consistent with the 1975 Declaration of Helsinki. Medical histories of the enrolled participants were recorded in detail, and all the participants received physical examinations. The diagnostic criteria for sporadic OC patients were those of FIGO (Federation International of Gynecology and Obstetrics) and the patients had no history of other systemic abnormalities or previous tumor or familial history of tumor. The exclusion criteria for the control participants were any diseases or systemic abnormalities. DNA analysis We used standard protocols to extract the genomic DNA from the peripheral blood leukocytes as described previously [ 29 ]. The CXCL1 gene was amplified by PCR with the primers shown in Table 2. PCR products were sequenced using standard protocols [ 30 , 31 ] for genotype analysis. SNP genotyping and statistical analysis The variations within or near the CXCL1 gene were determined for the 300 sporadic OC cases and 400 normal controls. The DNA regions were amplified and the PCR products were sequenced to determine the genotypes; two researchers conducted the measurements independently. Overall OC genetics correlation analysis was also conducted. As previously reported, the statistical analyses and Hardy–Weinberg equilibrium tests of the patients and control populations were conducted [ 29 , 32-34 ]. Results Clinical data The clinical diagnosis of all the participants was confirmed by specialists in Department of Gynaecology and Obstetrics in the Second Affiliated Hospital of Harbin Medical University, Harbin, China. These OC patients had no history of other systemic abnormalities or previous tumor or familial history of tumor. All the OC patients (n = 300, female, average age was 50.39 years, the min and max age were 18 and 81 respectively) and normal controls (n = 400, female, the average age was 49.68, the min and max age were 31 and 67 respectively) were recruited specifically for this study. There were no statistical differences in age composition between the two groups (Table 1). SNP gene analyses In order to test the hypothesis that germline common genetic variants in CXCL1 gene may be associated with the susceptibility to OC, we extracted the genomic DNA from the peripheral blood leukocytes of the participants and sequenced the CXCL1 gene to detect SNPs. We found six SNPs distributed on the gene, including rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 (Fig 1A). Analysis of these SNPs showed that the genetic heterozygosity of rs11547681 and rs4074 was very high (Fig 1B), whereas that of rs201090116, rs199791199, rs181868085 and rs1814092 was very low and were excluded from further analysis. Polymorphism-disease association analyses To test the hypothesized associations between CXCL1 variations and OC, we conducted analyses on the SNPs and found the variant rs11547681 within the 5’UTR of the gene was associated with the risk of OC in the Chinese Han population (Tables 3 and 4). Further, we analyzed the Hardy–Weinberg equilibrium test for the study population groups, and it was in line with equilibrium (Table 5). The genotype frequencies in the two groups were also analyzed by three genetic models (trend, dominant and recessive), and we found that the rs11547681 was associated with the risk of OC in trend and dominant models (Table 6). For the variant rs4074, we did not find statistical significance between the OC and control groups (chi-square tests; trend, dominant and recessive models). We compared the genotype frequency of the rs11547681 and rs4074 in the two groups and the data from the HapMap HCB population, but did not find the genotype frequency data of rs11547681 in the HapMap HCB population. Clinical features comparative analysis We also compared the clinical characteristics between the wild type, heterozygous variant and homozygous variant groups of the OC patients, but did not find statistically significant differences between the three groups in FIGO stages and pathological grades (Table 7). Discussion In this study, we found that the SNP rs11547681 within the 5’UTR of CXCL1 gene was associated with OC. The microenvironment of tumors is an important factor in modulating cancer development, especially in organs that communicates with the outside environment [ 35 , 36 ]. The cells surrounding those tumors usually release some factors, such as growth or inflammatory factors, which may regulate inflammation or progression of tumors [ 37 , 38 ]. The human chemokines have strong activities on tumor cells, especially in cross talk of tumor cells and their host microenvironment [ 39 ]. CXCL1 is one member of the chemokines, which is a proinflammatory mediator in many inflammatory diseases. CXCL1 promotes and exacerbates growth and progression of many tumors [ 40 ]. By activating CXCR2, CXCL1 is associated with cancer cell growth and proliferation, tumor angiogenesis and metastasis [ 41 , 42 ]. In tumor therapies, CXCL1 is also responsible for resistance of the cancer cells to several chemotherapeutic drugs [ 43 ]. In the OC cells, over-expression of the CXCL1 factor promotes the abilities of cellular proliferation and invasion in vitro [ 27 , 44 ]. Progesterone and calcitriol can inhibit ovarian and endometrial cancer cell growth by attenuating the functions of CXCL1; if the expression of CXCL1 is reduced, the inhibitory effect of the two agents is also abrogated [ 45 ]. Conversely, when the expression of CXCL1 is increased, the activation of metastasis promoting gene p65 is also increased in OC cells [ 45 ]. The serum CXCL1 may be a novel tumor marker for OC diagnosis [ 46 ]. In this study, we found that the SNP rs11547681 in the CXCL1 gene was associated with OC. This finding provides novel insights into the special roles of CXCL1 factor for the pathogenesis, diagnosis and therapies of ovarian cancer. Many chemokines exist as monomers or dimers in vivo. They function by binding to tissue glycosaminoglycans (GAGs) heparan sulfate (HS), chondroitin sulfate (CS) or dermatan sulfate (DS) [ 47 , 48 ]. GAGs bind to a diversity of protein classes [ 49 ], so in order to interact with GAGs, the sequence of chemokine must determine the selectivity, affinity and geometry [ 50 ]. CXCL1 belong to the CXC chemokines subset, characterized by the N-terminal‘ELR’motifs [ 51 ]. The amino acid residues located within the N terminal loop and C terminal helix of CXCL1 factor mediate HS binding, and the participation of other residues may result in a very different binding geometry for CXCL1 [ 50 ]. The SNP rs11547681 associated with OC is located within the 5’UTR of CX CL1 gene. The 5’UTR and 3’UTR sequences regulate expression of genes [ 52 , 53 ]. The 5’UTR sequences of gene bind with miRNAs and may be involved in gene expression, protein translation or disease pathogenesis [ 54 ]. In previous studies, we reported SNPs within the 5’UTR or 3’UTR sequences that are associated with diseases [ 31 , 32 , 55 ]. The results of this work further emphasized the important roles of 5’UTR sequences for CXCL1 factor functions. In conclusion, we demonstrated the associations of CXCL1 variants rs11547681 with the risk of ovarian cancer in the Chinese Han population and updated our understanding on 5’UTR for CXCL1 functions, providing new information on the pathogenesis of cancers especially ovarian cancer. Declarations Author Contributions: Conceptualization: FF L, SL L; methodology: FF L, SL L, M G, C X; software: FF L, SL L, C X; formal analysis: FF L, SL L, M G, C X; investigation: M G, C X, YZ C, QW S, Y Y, YH H; resources: M G; data curation: FF L, SL L, M G, C X; writing: FF L, SL L; funding acquisition: FF L, SL L Acknowledgements: The authors thank the patients and their families for their cooperation and participation in this study. Competing Interests: All the authors have declared that no competing interests exist. Financial disclosures: There are no financial disclosures from any authors. Availability of data and materials: The datasets used in the present study are available from the corresponding authors with reasonable requests. Consent for publication: Not applicable. Funding Statement: This work was supported by grants from Health and Family Planning Commission of Heilongjiang province Foundation (2017-077), Postdoctoral Foundaction of Heilongjiang Province and grants of National Natural Science Foundation of China (NSFC81271786, 81030029, 81671980, 81871623), Heilongjiang Innovation Research Foundation for College Students (201810226070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ethics approval: Ethics Committee of Harbin Medical University. Informed consent: Informed consent was obtained from all individual participants. Author details: 1 Genomics Research Center, College of Pharmacy (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China; 2 Department of Gynaecology and Obstetrics of the Second Affiliated Hospital,Harbin Medical University, Harbin, China; 3 Department of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin, China; 4 Department of Blood Dialysis, Heilongjiang Agricultural Reclamation Bureau General Hospital, Harbin, China. 5 Fifth hospital gynecology the city of Xiamen, Fujian, China; 6 Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China; 7 Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada References Webb PM, Jordan SJ: Epidemiology of epithelial ovarian cancer . Best Pract Res Clin Obstet Gynaecol 2017, 41 :3-14. 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Parameter CRC Control F t P 95%CI Up Low Sample (n) 300 400 - - - - - Age (years) 50.39±12.21 49.68±7.66 9.977 0.639 0.523 -1.47926 2.90141 Data are shown as mean ± SD; between the two groups, there were no statistical differences of the age and gender composition Table 2 : PCR primers used for CXCL1 gene sequence analysis Exon Forward primer Reverse primer Size(bp) Tm (℃) Exon1 GCGGGCTGCATCAGTGGA CGGGACTTACATGACTTCGGT 595 59.8 Exon2 CTGCTGCTCCTGCTCCTGGTA GGAAGGGAATCTCGTGAGGC 370 59.4 Exon3 AAACCGAAGTCATGTAAGTCC CAATAATCCCAATTTCTAGTCC 336 54.0 Exon4a TTAGAGGTCCCTGCCACA ATTCCCCTGCCTTCACAA 629 52.2 Exon4b TGCAACATGCCAGCCACT ATAGCAAATTGAACACCC 460 50.0 Table3: The genotype and allele frequency of variations in 300 Chinese Han ovarian cancer patients and 400 normal controls. SNP Group Genotype frequency (%) Allele frequency (%) rs11547681 Genotype G/G G/T T/T G T OC 300 185 (61.7) 107 (35.7) 8 (2.7) 477 (79.5) 123 (20.5) Controls 400 294 (73.5) 94 (23.5) 12 (3.0) 682 (85.3) 118 (14.8) rs4074 Genotype G/G G/A A/A G A OC 300 84 (28.0) 153 (51.0) 63 (21.0) 321 (53.5) 279 (46.5) Controls 400 120 (30.0) 207 (51.8) 73 (18.3) 447 (55.9) 353 (44.1) Note: OC= Ovarian Cancer Table4: rs11547681 variations within 5’UTR of the CXCL1 gene associated with risk of ovarian cancer in Chinese populations Variations Type Pearson Chi-square Risk Value Min count df Asymp. Sig. (2-sided) Value 95% CI-low 95% CI-up rs11547681 Genotype 12.412 8.57 2 0.002* - - - Allele 7.954 103.29 1 0.005* 0.671 0.508 0.886 rs4074 Genotype 0.921 58.29 2 0.631 - - - Allele 0.781 270.86 1 0.377 0.909 0.735 1.124 *: statistically significant Table 5: Hardy-Weinberg equilibrium test for the study population groups SNPs Genotype H-W equilibrium Testing Homo/Hetero/Homozygote O(HET) E (HET) P rs11547681 OC 8/107/185 0.3567 0.3259 0.1541 Controls 12/94/294 0.2350 0.2515 0.2292 rs4074 OC 63/153/84 0.5100 0.4975 0.7281 Controls 73/207/120 05175 0.4931 0.3618 Note: OC= Ovarian Cancer Table 6: SNP rs11547681 within CXCL1 gene associated with the risk of ovarian cancer SNPs Value Trend model Dominant model Recessive model rs11547681 ChisQ 8.0140 11.1100 0.0686 P 0.0046* 0.0009* 0.7933 rs4074 ChisQ 0.8121 0.3321 0.8282 P 0.3675 0.5644 0.3628 *: statistically significant Table7: Comparative analysis of clinical features between wild type, heterozygous variation and homozygous variation groups Clinical Index Wild Type heterozygous variation homozygous variation Chi-Square Test TNM Stage ( Ⅰ / Ⅱ / Ⅲ / Ⅳ ) 59/32/92/2 30/23/54/1 2/1/5/0 P=0.956 Pathological Grades(H/M/L/Non) 101/15/36/33 54/7/31/15 5/0/3/0 P=0.375 H: Pathological high Grade; M: Pathological moderately Grade; L: Pathological low Grade; Non: No pathological grade. Cite Share Download PDF Status: Published Journal Publication published 23 Apr, 2020 Read the published version in Journal of Ovarian Research → Version 4 posted Editor assigned by journal 27 Mar, 2020 Editorial decision: Accept 27 Mar, 2020 Submission checks completed at journal 26 Mar, 2020 Editor invited by journal 26 Mar, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9270","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":450480,"identity":"93cef60c-5e2e-4f75-b7e2-0a84a7186563","order_by":1,"name":"Man Guo","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Man","middleName":"","lastName":"Guo","suffix":""},{"id":450481,"identity":"ea349097-0695-4a5f-8380-40147672a51c","order_by":2,"name":"Chao Xu","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Xu","suffix":""},{"id":450482,"identity":"cd1dd4e9-8f34-4a19-a7ed-793fb890fc57","order_by":3,"name":"Yan-Zhe Chen","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan-Zhe","middleName":"","lastName":"Chen","suffix":""},{"id":450483,"identity":"699593ca-8988-4f05-90ca-0e01a9e883e5","order_by":4,"name":"Qi-Wen Sun","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qi-Wen","middleName":"","lastName":"Sun","suffix":""},{"id":450484,"identity":"9d2cdb20-f3f7-4c88-b2b7-2735ebaa164f","order_by":5,"name":"Xin-Ying Zhao","email":"","orcid":"","institution":"Heilongjiang Agricultural Reclamation Bureau General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xin-Ying","middleName":"","lastName":"Zhao","suffix":""},{"id":450485,"identity":"7d61d583-272a-44cd-ac91-73dfaf91e5f1","order_by":6,"name":"Xin Liu","email":"","orcid":"","institution":"fifth hospital gynecology the city of Xiamen","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Liu","suffix":""},{"id":450486,"identity":"7665fa06-1769-4a59-997a-0b10069f94c6","order_by":7,"name":"Yi Yang","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Yang","suffix":""},{"id":450487,"identity":"a7a36b43-ab69-4b40-8b7d-b75330de05aa","order_by":8,"name":"Yi-Yan Hu","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yi-Yan","middleName":"","lastName":"Hu","suffix":""},{"id":450488,"identity":"454652ef-75cb-42f1-b321-389ca45d60aa","order_by":9,"name":"Fei-Feng Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIie3QsQrCQAyA4ZSDm2JvrSDoIwQKTgc+iMuJcJurdOhQEOrYV6oEdCn6CucbOHa0uDlIr5tD/jkfIQGQpD8sVZcArrBolOIQRbTeE4TOL+Zn7SmaJM+aLT1wlUUSBbCrPeaMQFDabRxxd4trnrUBrv5QjZJlc+vd0Q8kdZRUHEE+WzRjfkLKJpCakdQ00nnMeHiyi7nFDCTpC7sxDXN4lXacfOemjUuSJEm/egNbRTTm8P0BvgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-7056-6101","institution":"Harbin Medical University","correspondingAuthor":true,"prefix":"","firstName":"Fei-Feng","middleName":"","lastName":"Li","suffix":""},{"id":450489,"identity":"0fd14dc2-d21c-46c5-99f5-5c4a965661ce","order_by":10,"name":"Shu-Lin Liu","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shu-Lin","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2019-12-08 14:44:59","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.2.18650/v4","doiUrl":"https://doi.org/10.21203/rs.2.18650/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13048-020-00640-9","type":"published","date":"2020-04-23T20:24:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":811967,"identity":"0fb5d426-d8fb-409d-8f78-2308209ed924","added_by":"auto","created_at":"2020-04-01 10:35:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":819000,"visible":true,"origin":"","legend":"Schematic diagrams and DNA sequence chromatogram of SNPs in CXCL1 gene. A: locations of rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within the CXCL1 gene; B: DNA sequence chromatogram of the three polymorphisms identified in the CXCL1 gene in all the population used for disease-association analyses.","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9270/v4/Figure 1.png"},{"id":13496186,"identity":"475d4100-b35f-4d50-b551-011b0d68ad92","added_by":"auto","created_at":"2021-09-16 22:48:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2215318,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9270/v4/5413f011-9515-4eb3-a94d-083ab04e80df.pdf"}],"financialInterests":"","formattedTitle":"Associations of CXCL1 gene 5’UTR variations with ovarian cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlobally, there are about 2.4 hundred thousand new ovarian cancer (OC) cases and about 1.5 hundred thousand deaths caused by this disease annually [\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e]. OC is the 7th most common and 5\u003csup\u003eth\u003c/sup\u003e most lethal cancer among women worldwide [\u003ca href=\"#_ENREF_2\"\u003e2\u003c/a\u003e]. The incidence rates of OC are highest in northern and eastern Europe, and lowest in Asia and Africa [\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e]. In the past decades, however, the morbidity has considerably decreased in many previously high incidence countries but, in contrast, is increasing in some low incidence countries, such as China [\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e, \u003ca href=\"#_ENREF_3\"\u003e3\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eThe 5-years survival rates of OC range from 30.3% to 44.1%, depending on the specific subtypes and stages at the time of diagnosis or treatment [\u003ca href=\"#_ENREF_4\"\u003e4\u003c/a\u003e, \u003ca href=\"#_ENREF_5\"\u003e5\u003c/a\u003e]. Early detection and treatment of this disease can significantly increase the survival rate of OC, but, due to the lack of specific signs or symptoms at early stages, this disease is usually diagnosed only at late stages [\u003ca href=\"#_ENREF_6\"\u003e6\u003c/a\u003e]. The recurrence rate of this disease is also very high, often leading to death of the patient, who might have achieved a clinical complete remission after primary therapy [\u003ca href=\"#_ENREF_5\"\u003e5\u003c/a\u003e, \u003ca href=\"#_ENREF_6\"\u003e6\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eSo far, several genetic and non-genetic factors have been found to be associated with OC. Women with affected first-degree relatives usually have higher risks for OC [\u003ca href=\"#_ENREF_7\"\u003e7\u003c/a\u003e], and women, who have relatives diagnosed with OC below 50 years old, have even higher OC risks [\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e]. Many gene mutations have been associated with sporadic OC patients, including BRCA1 and 2 [\u003ca href=\"#_ENREF_9\"\u003e9\u003c/a\u003e], BRIP1 [\u003ca href=\"#_ENREF_10\"\u003e10\u003c/a\u003e] and RAD51 [\u003ca href=\"#_ENREF_11\"\u003e11\u003c/a\u003e]. Oral contraceptive use and tubal ligation seem to be protective factors [\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e, \u003ca href=\"#_ENREF_13\"\u003e13\u003c/a\u003e], whereas older menopausal ages, obesity, menopausal hormone therapy use, a history of endometriosis and smoking are all risk factors [\u003ca href=\"#_ENREF_14\"\u003e14-16\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eChronic inflammation, such as those caused by asbestos or talc exposure, endometriosis or pelvic inflammatory diseases, has also been suggested to be a risk factor for OC [\u003ca href=\"#_ENREF_17\"\u003e17\u003c/a\u003e, \u003ca href=\"#_ENREF_18\"\u003e18\u003c/a\u003e]. On the other side, anti-inflammatory medications, e.g., acetaminophen and low-dose of aspirin are protective factors for OC [\u003ca href=\"#_ENREF_19\"\u003e19\u003c/a\u003e, \u003ca href=\"#_ENREF_20\"\u003e20\u003c/a\u003e]. Immunotherapies, including immune checkpoint blockade and cancer vaccines, also have many special roles in immune recognition and immune regulation of the OC cells [\u003ca href=\"#_ENREF_21\"\u003e21\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eChemokines expressed in tumor or stromal cells may facilitate tumor angiogenesis and in the meantime suppress immune-mediated tumor elimination, and as a result are associated with cancers [\u003ca href=\"#_ENREF_22\"\u003e22-24\u003c/a\u003e]. C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC subfamily of chemokines and an oncogenic factor in many cancers [\u003ca href=\"#_ENREF_25\"\u003e25\u003c/a\u003e, \u003ca href=\"#_ENREF_26\"\u003e26\u003c/a\u003e]. It can transactivate EGFR in OC through binding to the G-protein coupled receptor CXC receptor 2 (CXCR2) [\u003ca href=\"#_ENREF_27\"\u003e27\u003c/a\u003e]. Abnormal expression of CXCL1 is associated with many tumors [\u003ca href=\"#_ENREF_28\"\u003e28\u003c/a\u003e], but the associated haplotypes remained largely unknown.\u003c/p\u003e\n\u003cp\u003eIn this work, we investigated variants in the \u003cem\u003eCXCL1\u003c/em\u003e gene for their associations with the risk of OC in the Chinese Han population. We found that variant rs11547681 was associated with ovarian cancer and demonstrated the 5\u0026rsquo;UTR for the functions of CXCL1.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 300 sporadic OC cases and 400 normal controls (Table 1) were assembled for this study at the Department of Gynaecology and Obstetrics and Medical Examination Center of the Second Affiliated Hospital of Harbin Medical University, Harbin, China. From each participant, we obtained a written informed consent. This work has been reviewed and approved by the Ethics Committee of Harbin Medical University. We also confirmed that all experiments were performed in accordance with relevant guidelines and regulations and were consistent with the 1975 Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eMedical histories of the enrolled participants were recorded in detail, and all the participants received physical examinations. The diagnostic criteria for sporadic OC patients were those of FIGO (Federation International of Gynecology and Obstetrics) and the patients had no history of other systemic abnormalities or previous tumor or familial history of tumor. The exclusion criteria for the control participants were any diseases or systemic abnormalities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDNA analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used standard protocols to extract the genomic DNA from the peripheral blood leukocytes as described previously [\u003ca href=\"#_ENREF_29\"\u003e29\u003c/a\u003e]. The \u003cem\u003eCXCL1\u003c/em\u003e gene was amplified by PCR with the primers shown in Table 2. PCR products were sequenced using standard protocols [\u003ca href=\"#_ENREF_30\"\u003e30\u003c/a\u003e, \u003ca href=\"#_ENREF_31\"\u003e31\u003c/a\u003e] for genotype analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSNP genotyping and statistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe variations within or near the \u003cem\u003eCXCL1 \u003c/em\u003egene were determined for the 300 sporadic OC cases and 400 normal controls. The DNA regions were amplified and the PCR products were sequenced to determine the genotypes; two researchers conducted the measurements independently. Overall OC genetics correlation analysis was also conducted. As previously reported, the statistical analyses and Hardy\u0026ndash;Weinberg equilibrium tests of the patients and control populations were conducted [\u003ca href=\"#_ENREF_29\"\u003e29\u003c/a\u003e, \u003ca href=\"#_ENREF_32\"\u003e32-34\u003c/a\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical diagnosis of all the participants was confirmed by specialists in Department of Gynaecology and Obstetrics in the Second Affiliated Hospital of Harbin Medical University, Harbin, China. These OC patients had no history of other systemic abnormalities or previous tumor or familial history of tumor. All the OC patients (n = 300, female, average age was 50.39 years, the min and max age were 18 and 81 respectively) and normal controls (n = 400, female, the average age was 49.68, the min and max age were 31 and 67 respectively) were recruited specifically for this study. There were no statistical differences in age composition between the two groups (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSNP gene analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn order to test the hypothesis that germline common genetic variants in \u003cem\u003eCXCL1\u003c/em\u003e gene may be associated with the susceptibility to OC, we extracted the genomic DNA from the peripheral blood leukocytes of the participants and sequenced the \u003cem\u003eCXCL1\u003c/em\u003e gene to detect SNPs. We found six SNPs distributed on the gene, including rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 (Fig 1A). Analysis of these SNPs showed that the genetic heterozygosity of rs11547681 and rs4074 was very high (Fig 1B), whereas that of rs201090116, rs199791199, rs181868085 and rs1814092 was very low and were excluded from further analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePolymorphism-disease association analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo test the hypothesized associations between \u003cem\u003eCXCL1\u003c/em\u003e variations and OC, we conducted analyses on the SNPs and found the variant rs11547681 within the 5\u0026rsquo;UTR of the gene was associated with the risk of OC in the Chinese Han population (Tables 3 and 4). Further, we analyzed the Hardy\u0026ndash;Weinberg equilibrium test for the study population groups, and it was in line with equilibrium (Table 5).\u003c/p\u003e\n\u003cp\u003eThe genotype frequencies in the two groups were also analyzed by three genetic models (trend, dominant and recessive), and we found that the rs11547681 was associated with the risk of OC in trend and dominant models (Table 6). For the variant rs4074, we did not find statistical significance between the OC and control groups (chi-square tests; trend, dominant and recessive models). We compared the genotype frequency of the rs11547681 and rs4074 in the two groups and the data from the HapMap HCB population, but did not find the genotype frequency data of rs11547681 in the HapMap HCB population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical features comparative analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe also compared the clinical characteristics between the wild type, heterozygous variant and homozygous variant groups of the OC patients, but did not find statistically significant differences between the three groups in FIGO stages and pathological\u0026nbsp;grades (Table 7).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that the SNP rs11547681 within the 5\u0026rsquo;UTR of \u003cem\u003eCXCL1\u003c/em\u003e gene was associated with OC. The microenvironment of tumors is an important factor in modulating cancer development, especially in organs that communicates with the outside environment [\u003ca href=\"#_ENREF_35\"\u003e35\u003c/a\u003e, \u003ca href=\"#_ENREF_36\"\u003e36\u003c/a\u003e]. The cells surrounding those tumors usually release some factors, such as growth or inflammatory factors, which may regulate inflammation or progression of tumors [\u003ca href=\"#_ENREF_37\"\u003e37\u003c/a\u003e, \u003ca href=\"#_ENREF_38\"\u003e38\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eThe human chemokines have strong activities on tumor cells, especially in cross talk of tumor cells and their host microenvironment [\u003ca href=\"#_ENREF_39\"\u003e39\u003c/a\u003e]. CXCL1 is one member of the chemokines, which is a proinflammatory mediator in many inflammatory diseases. CXCL1 promotes and exacerbates growth and progression of many tumors [\u003ca href=\"#_ENREF_40\"\u003e40\u003c/a\u003e]. By activating CXCR2, CXCL1 is associated with cancer cell growth and proliferation, tumor angiogenesis and metastasis [\u003ca href=\"#_ENREF_41\"\u003e41\u003c/a\u003e, \u003ca href=\"#_ENREF_42\"\u003e42\u003c/a\u003e]. In tumor therapies, CXCL1 is also responsible for resistance of the cancer cells to several chemotherapeutic drugs [\u003ca href=\"#_ENREF_43\"\u003e43\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003eIn the OC cells, over-expression of the CXCL1 factor promotes the abilities of cellular proliferation and invasion in vitro [\u003ca href=\"#_ENREF_27\"\u003e27\u003c/a\u003e, \u003ca href=\"#_ENREF_44\"\u003e44\u003c/a\u003e]. Progesterone and calcitriol can inhibit ovarian and endometrial cancer cell growth by attenuating the functions of CXCL1; if the expression of CXCL1 is reduced, the inhibitory effect of the two agents is also abrogated [\u003ca href=\"#_ENREF_45\"\u003e45\u003c/a\u003e]. Conversely, when the expression of CXCL1 is increased, the activation of metastasis promoting gene p65 is also increased in OC cells [\u003ca href=\"#_ENREF_45\"\u003e45\u003c/a\u003e]. The serum CXCL1 may be a novel tumor marker for OC diagnosis [\u003ca href=\"#_ENREF_46\"\u003e46\u003c/a\u003e]. In this study, we found that the SNP rs11547681 in the \u003cem\u003eCXCL1\u003c/em\u003e gene was associated with OC. This finding provides novel insights into the special roles of CXCL1 factor for the pathogenesis, diagnosis and therapies of ovarian cancer.\u003c/p\u003e\n\u003cp\u003eMany chemokines exist as monomers or dimers in vivo. They function by binding to tissue glycosaminoglycans (GAGs) heparan sulfate (HS), chondroitin sulfate (CS) or dermatan sulfate (DS) [\u003ca href=\"#_ENREF_47\"\u003e47\u003c/a\u003e, \u003ca href=\"#_ENREF_48\"\u003e48\u003c/a\u003e]. GAGs bind to a diversity of protein classes [\u003ca href=\"#_ENREF_49\"\u003e49\u003c/a\u003e], so in order to interact with GAGs, the sequence of chemokine must determine the selectivity, affinity and geometry [\u003ca href=\"#_ENREF_50\"\u003e50\u003c/a\u003e]. CXCL1 belong to the CXC chemokines subset, characterized by the N-terminal\u0026lsquo;ELR\u0026rsquo;motifs [\u003ca href=\"#_ENREF_51\"\u003e51\u003c/a\u003e]. The amino acid residues located within the N terminal loop and C terminal helix of CXCL1 factor mediate HS binding, and the participation of other residues may result in a very different binding geometry for CXCL1 [\u003ca href=\"#_ENREF_50\"\u003e50\u003c/a\u003e]. The SNP rs11547681 associated with OC is located within the 5\u0026rsquo;UTR of CX\u003cem\u003eCL1\u003c/em\u003e gene. The 5\u0026rsquo;UTR and 3\u0026rsquo;UTR sequences regulate expression of genes [\u003ca href=\"#_ENREF_52\"\u003e52\u003c/a\u003e, \u003ca href=\"#_ENREF_53\"\u003e53\u003c/a\u003e]. The 5\u0026rsquo;UTR sequences of gene bind with miRNAs and may be involved in gene expression, protein translation or disease pathogenesis [\u003ca href=\"#_ENREF_54\"\u003e54\u003c/a\u003e]. In previous studies, we reported SNPs within the 5\u0026rsquo;UTR or 3\u0026rsquo;UTR sequences that are associated with diseases [\u003ca href=\"#_ENREF_31\"\u003e31\u003c/a\u003e, \u003ca href=\"#_ENREF_32\"\u003e32\u003c/a\u003e, \u003ca href=\"#_ENREF_55\"\u003e55\u003c/a\u003e]. The results of this work further emphasized the important roles of 5\u0026rsquo;UTR sequences for CXCL1 factor functions.\u003c/p\u003e\n\u003cp\u003eIn conclusion, we demonstrated the associations of \u003cem\u003eCXCL1\u003c/em\u003e variants rs11547681 with the risk of ovarian cancer in the Chinese Han population and updated our understanding on 5\u0026rsquo;UTR for CXCL1 functions, providing new information on the pathogenesis of cancers especially ovarian cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Conceptualization: FF L, SL L; methodology: FF L, SL L, M G, C X; software: FF L, SL L, C X; formal analysis: FF L, SL L, M G, C X; investigation: M G, C X, YZ C, QW S, Y Y, YH H; resources: M G; data curation: FF L, SL L, M G, C X; writing: FF L, SL L; funding acquisition: FF L, SL L\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements: \u003c/strong\u003eThe authors thank the patients and their families for their cooperation and participation in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e All the authors have declared that no competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures:\u003c/strong\u003e There are no financial disclosures from any authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials: \u003c/strong\u003eThe datasets used in the present study are available from the corresponding authors with reasonable requests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication: \u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement:\u003c/strong\u003e This work was supported by grants from Health and Family Planning Commission of Heilongjiang province Foundation (2017-077), Postdoctoral Foundaction of Heilongjiang Province and grants of National Natural Science Foundation of China (NSFC81271786, 81030029, 81671980, 81871623), Heilongjiang Innovation Research Foundation for College Students (201810226070). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e Ethics Committee of Harbin Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e Informed consent was obtained from all individual participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details: \u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003eGenomics Research Center, College of Pharmacy (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China; \u003csup\u003e2\u003c/sup\u003eDepartment of Gynaecology and Obstetrics of the Second Affiliated Hospital,Harbin Medical University, Harbin, China; \u003csup\u003e3\u003c/sup\u003eDepartment of Colorectal Surgery of the Second Affiliated Hospital, Harbin Medical University, Harbin, China;\u003csup\u003e4\u003c/sup\u003eDepartment\u0026nbsp;of\u0026nbsp;Blood\u0026nbsp;Dialysis,\u0026nbsp;Heilongjiang\u0026nbsp;Agricultural\u0026nbsp;Reclamation\u0026nbsp;Bureau\u0026nbsp;General\u0026nbsp;Hospital,\u0026nbsp;Harbin,\u0026nbsp;China. \u003csup\u003e5\u003c/sup\u003eFifth hospital gynecology the city of Xiamen, Fujian, China; \u003csup\u003e6\u003c/sup\u003eTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Heilongjiang, China; \u0026nbsp;\u003csup\u003e7\u003c/sup\u003eDepartment of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWebb PM, Jordan SJ: \u003cstrong\u003eEpidemiology of epithelial ovarian cancer\u003c/strong\u003e. \u003cem\u003eBest Pract Res Clin Obstet Gynaecol \u003c/em\u003e2017, \u003cstrong\u003e41\u003c/strong\u003e:3-14.\u003c/li\u003e\n\u003cli\u003eTorre LA, 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\u003cstrong\u003e18\u003c/strong\u003e(17):2444-2452.\u003c/li\u003e\n\u003cli\u003eFujimuro T, Matsui T, Nitanda Y, Matta T, Sakumura Y, Saito M, Kohno K, Nakahata Y, Bessho Y: \u003cstrong\u003eHes7 3'UTR is required for somite segmentation function\u003c/strong\u003e. \u003cem\u003eSci Rep \u003c/em\u003e2014, \u003cstrong\u003e4\u003c/strong\u003e:6462.\u003c/li\u003e\n\u003cli\u003eOrom UA, Nielsen FC, Lund AH: \u003cstrong\u003eMicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation\u003c/strong\u003e. \u003cem\u003eMol Cell \u003c/em\u003e2008, \u003cstrong\u003e30\u003c/strong\u003e(4):460-471.\u003c/li\u003e\n\u003cli\u003eLi FF, Han Y, Shi S, Li X, Zhu XD, Zhou J, Shao QL, Li XQ, Liu SL: \u003cstrong\u003eCharacterization of Transcriptional Repressor Gene MSX1 Variations for Possible Associations with Congenital Heart Diseases\u003c/strong\u003e. \u003cem\u003ePLoS One \u003c/em\u003e2015, \u003cstrong\u003e10\u003c/strong\u003e(11):e0142666.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12px; line-height: 150%; color: rgb(0, 0, 0); font-family: Helvetica;\"\u003eTable1: Clinical characteristics of study population.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"float: left;width: 714;border-collapse:collapse;border:none;margin-left:6.75pt;margin-right: 6.75pt;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 121.5pt;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eParameter\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71.85pt;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eCRC\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 71.85pt;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eControl\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0.75in;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eF\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0.75in;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003et\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 0.75in;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eP\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 1.5in;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 24.9pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003e95%CI\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;height: 26.5pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eUp\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: 1.5pt solid black;border-left: none;border-bottom: 1.5pt solid black;border-right: none;padding: 0in 5.4pt;height: 26.5pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eLow\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121.5pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eSample (n)\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.85pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e300\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.85pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e400\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eAge (years)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e50.39±12.21\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e49.68±7.66\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e9.977\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.639\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.523\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-1.47926\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.75in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1.5pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2.90141\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eData are shown as mean ± SD; between the two groups, there were no statistical differences of the age and gender composition\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\n \u003cbr\u003e\n\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e: PCR primers used for\u003cem\u003e\u0026nbsp;CXCL1\u0026nbsp;\u003c/em\u003egene sequence analysis\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\n \u003ctable style=\"width: 700;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eForward primer\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eReverse primer\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eSize(bp)\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eTm (℃)\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon1\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eGCGGGCTGCATCAGTGGA\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eCGGGACTTACATGACTTCGGT\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e595\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e59.8\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon2\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eCTGCTGCTCCTGCTCCTGGTA\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eGGAAGGGAATCTCGTGAGGC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e370\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e59.4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon3\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eAAACCGAAGTCATGTAAGTCC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eCAATAATCCCAATTTCTAGTCC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e336\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e54.0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon4a\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eTTAGAGGTCCCTGCCACA\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eATTCCCCTGCCTTCACAA\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e629\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e52.2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:76.5pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height:150%;\"\u003eExon4b\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:169.85pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eTGCAACATGCCAGCCACT\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:2.5in;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eATAGCAAATTGAACACCC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.95pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e460\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:50.9pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003e50.0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\n \u003cbr\u003e\n\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable3:\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eThe genotype and allele frequency of variations in 300 Chinese Han\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eovarian cancer\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;patients and 400 normal controls.\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 669;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:94.5pt;border:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.6pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eSNP\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:94.5pt;border:solid black 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:42.6pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eGroup\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:184.95pt;border:solid black 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:42.6pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eGenotype frequency (%)\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:127.6pt;border:solid black 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:42.6pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eAllele frequency (%)\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:94.5pt;border:solid black 1.0pt;border-top:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers11547681\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:94.5pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eGenotype\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eG/G\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp 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style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eT\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eOC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:31.5pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e300\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e185 (61.7)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e107 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style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e477 (79.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e123 (20.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eControls\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:31.5pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e400\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e294 (73.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e94 (23.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:58.95pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e12 (3.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e682 (85.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e118 (14.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:94.5pt;border:solid black 1.0pt;border-top:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers4074\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:94.5pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eGenotype\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eG/G\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eG/A\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:58.95pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eA/A\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eG\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eA\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eOC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:31.5pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e300\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e84 (28.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e153 (51.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:58.95pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e63 (21.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e321 (53.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e279 (46.5)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eControls\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:31.5pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e400\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e120 (30.0)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.0pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e207 (51.8)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:58.95pt;border-top:none;border-left:none;border-bottom:solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e73 (18.3)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e447 (55.9)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border-top:none;border-left:none;border-bottom: solid black 1.0pt;border-right:solid black 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e353 (44.1)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eNote:\u0026nbsp;OC= Ovarian Cancer\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cstrong style=\"font-size: 12px; font-family: Helvetica; text-align: justify;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable4:\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cstrong style=\"font-size: 12px; font-family: Helvetica; text-align: justify;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003ers11547681\u003c/span\u003e\u003c/strong\u003e\u003cstrong style=\"font-size: 12px; font-family: Helvetica; text-align: justify;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;variations within 5’UTR of the \u003cem\u003eCXCL1\u0026nbsp;\u003c/em\u003e\u003c/span\u003e\u003c/strong\u003e\u003cstrong style=\"font-size: 12px; font-family: Helvetica; text-align: justify;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003egene associated with risk of ovarian cancer in Chinese populations\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\" style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\n \u003ctable style=\"width:429.85pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:67.85pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eVariations\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:57.5pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eType\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width:166.15pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ePearson Chi-square\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:138.35pt;border-top:solid black 1.5pt;border-left:none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003eRisk\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:47.4pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:46.15pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eValue\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:46.15pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eMin count\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:20.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:46.15pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003edf\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:54.15pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:46.15pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eAsymp. 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Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e95% CI-low \u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.0pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:46.15pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e95% CI-up\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n 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style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eGenotype\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.4pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e12.412\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e8.57\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:20.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:54.15pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.002*\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New 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Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.886\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:67.85pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers4074\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n 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12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.921\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e58.29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:20.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:54.15pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.631\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:48.0pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.0pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:57.5pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eAllele\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:47.4pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.781\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:43.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e270.86\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:20.8pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:54.15pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.377\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:41.35pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.909\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:48.0pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0.735\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:49.0pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e1.124\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e*: statistically significant\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 200%;\"\u003eTable 5:\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 200%;\"\u003eHardy-Weinberg equilibrium test for the study population groups\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:69.75pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003eSNPs\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:145.25pt;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003eGenotype\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:214.2pt;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003eH-W equilibrium Testing\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width:145.25pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eHomo/Hetero/Homozygote\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:72.3pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eO(HET)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eE (HET)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.75pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers11547681\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:52.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eOC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e8/107/185\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:72.3pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.3567\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.3259\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.1541\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.75pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:52.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eControls\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e12/94/294\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:72.3pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.2350\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.2515\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.2292\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.75pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003ers4074\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:52.15pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eOC\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e63/153/84\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:72.3pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.5100\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.4975\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.7281\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:69.75pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:52.15pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eControls\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:93.1pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e73/207/120\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:72.3pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e05175\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.4931\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003e0.3618\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eNote:\u0026nbsp;OC= Ovarian Cancer\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 200%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\n \u003cbr\u003e\n\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:200%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height: 200%;\"\u003eTable 6: SNP rs11547681 within \u003cem\u003eCXCL1\u003c/em\u003e gene associated with the risk of ovarian cancer\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 485;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:77.55pt;border-top:solid black 1.0pt;border-left: none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003eSNPs\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:38.45pt;border-top:solid black 1.0pt;border-left: none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003eValue\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.85pt;border-top:solid black 1.0pt;border-left: none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003eTrend model\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:85.05pt;border-top:solid black 1.0pt;border-left: none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003eDominant model\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:92.1pt;border-top:solid black 1.0pt;border-left: none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cem\u003eRecessive model\u003c/em\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:77.55pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers11547681\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:38.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eChisQ\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e8.0140\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:85.05pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e11.1100\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:92.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.0686\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:38.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.0046*\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:85.05pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.0009*\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:92.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.7933\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:77.55pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style=\"line-height: 150%;\"\u003ers4074\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:38.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eChisQ\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.85pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.8121\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:85.05pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.3321\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:92.1pt;border:none;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.8282\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:38.45pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:70.85pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.3675\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:85.05pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.5644\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:92.1pt;border:none;border-bottom:solid black 1.5pt;padding:0in 5.4pt 0in 5.4pt;height:18.45pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e0.3628\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e*: statistically significant\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable7:\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;Comparative analysis of clinical features between wild type, heterozygous variation and homozygous variation groups\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:493.05pt;margin-left:-22.95pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:151.8pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:38.35pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003eClinical\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Index\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:84.25pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:38.35pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003eWild Type\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:86.8pt;border-top:solid black 1.5pt;border-left: none;border-bottom:solid black 1.5pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:38.35pt;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan 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solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;line-height:150%;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"line-height:150%;\"\u003eP=0.375\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"font-family: \n Helvetica;\"\u003e\u003cspan style=\"font-size: \n 12px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003eH: Pathological\u0026nbsp;high Grade; M: Pathological moderately Grade; L: Pathological low Grade; Non: No pathological\u0026nbsp;grade.\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\u0026quot;Times New Roman\u0026quot;,serif;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0); font-size: 12px; font-family: Helvetica;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ovarian cancer; Chronic inflammation; Chemokines; CXCL1; 5’UTR","lastPublishedDoi":"10.21203/rs.2.18650/v4","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.18650/v4","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC.\nMethods: We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9).\nResults: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients.\nConclusions: Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.","manuscriptTitle":"Associations of CXCL1 gene 5’UTR variations with ovarian cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-04-01 10:35:56","doi":"10.21203/rs.2.18650/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2020-03-27T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-03-27T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-26T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian 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policy.\n"},{"type":"reviewerAgreed","content":"","date":"2020-03-14T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-03-13T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-03-09T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-08T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-03-05 19:44:26","doi":"10.21203/rs.2.18650/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2020-03-03T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Major revision","date":"2020-03-03T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-02T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-02T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-12-15 23:35:32","doi":"10.21203/rs.2.18650/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-02-23T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-01-02T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2019-12-21T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-12-08T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-12-06T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-12-06T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-12-05T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-12-05T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3deffaea-2a44-4316-8165-f09160d5fe02","owner":[],"postedDate":"April 1st, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":70298,"name":"Cancer Biology"},{"id":70299,"name":"Sexual \u0026 Reproductive Medicine"}],"tags":[],"updatedAt":"2021-07-22T20:24:51+00:00","versionOfRecord":{"articleIdentity":"rs-9270","link":"https://doi.org/10.1186/s13048-020-00640-9","journal":{"identity":"journal-of-ovarian-research","isVorOnly":false,"title":"Journal of Ovarian Research"},"publishedOn":"2020-04-23 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