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Acad. Bras. Ciênc. 98 (suppl 1) • 2026 • https://doi.org/10.1590/0001-3765202620241498 link copy Investigation of the miRNA27a rs895819, miRNA222 rs2858060 and miRNA499a rs3746444 polymorphisms in Endometriosis Authorship SCIMAGO INSTITUTIONS RANKINGS Abstract The present study aimed to determine the allelic and genotypic frequencies of the miRNA27a rs895819, miRNA222 rs2858060 and miRNA499 rs3746444 polymorphisms and their possible association with endometriosis. This case-control study consisted of 143 women; 54 had endometriosis (case group) and 89 had no endometriosis (control group) ant the polymorphisms were determined by real-time PCR. For the statistical analysis, the chi-square was used to compare genotypic and allelic frequencies, estimate the Hardy-Weinberg equilibrium, and logistic regression test. There were no significant differences in genotype frequencies between case and control of miRNA27a rs895819 (X² = 2.57; p = 0.27) and of miRNA499a rs3746444 (χ2 = 3.65; p = 0.16), in other hand, exist a difference (X² = 8.42; p = 0.01) for miRNA222 rs2858060. Patients and controls were in Hardy-Weinberg equilibrium to rs895819, however to the polymorphisms rs2858060 and rs 3746444 were in disequilibrium to the controls. In the sample analyzed, the rs895819 polymorphism of miRNA-27a and the rs3746444 miRNA-499a are not associated with endometriosis, while the miRNA-222 rs2858060 displays a preliminary and exploratory indication of association. This work represents an advance in endometriosis genetics since it reveals a link between endometriosis and miRNA variants. Key words Biomarkers; Endometriosis; MicroRNAs; Polymorphism Genetic; Real-Time Polymerase Chain Reaction INTRODUCTION Endometriosis is characterized by endometrial-like tissue located outside the uterus. Symptoms include pelvic pain, painful sex, infertility, constipation, diarrhea, pain during defecation, severe period pain, heavy menstruation, fatigue, depression, and painful urination. These symptoms are also related to other conditions, and a definitive diagnosis of endometriosis requires surgery, leading to a delayed diagnosis (Saunders & Horne 2021 ). The World Health Organization (WHO) affirms it affects a significant number of women of reproductive age, i.e., more than 190 million have this disease (WHO 2023 ). Endometriosis is a chronic gynecological condition with a significant adverse effect on all aspects of the lives of affected women, impacting the quality of life, sexuality, causing psychological disorders (anxiety and depression), interfering with productivity at work, and having a significant economic impact (Bernardi et al. 2024 ). Early diagnosis is essential to prevent disease progression and preserve fertility. This backdrop creates a need for non-invasive diagnostic methods; therefore, many studies have been conducted searching for biomarkers that can help identify the most suitable treatment options for individual patients, leading to more personalized and effective care. Currently, microRNAs (miRNAs) have proven to be one of the best emerging diagnostic biomarkers with promising aid in terms of a non-invasive approach (Pant et al. 2023 ). The miRNAs are composed of 21-23 nucleotides and participate in RNA silencing and the regulation of gene expression post-transcriptionally. They play vital roles in a wide range of processes, including apoptosis, cell division, cell-to-cell signaling, and proliferation, and, for this reason, their expression is related to the pathogenesis of several diseases, such as cancer and gynecological diseases (Ghasemi et al. 2022 ). Besides that, the miRNAs can be involved in the progesterone resistance, inflammation, extracellular matrix remodeling, and angiogenesis, among other main processes of the endometriosis development (Ochoa Bernal & Fazleabas 2024). Therefore, identifying human disease-linked miRNAs would help to understand the pathogenesis of endometriosis. A recent systematic review included 32 articles, and a total of 141 miRNAs were significantly differentially expressed between endometriosis patients and controls. However, only 20 miRNAs were reported as dysregulated in endometriosis in two or more studies (Vanhie et al. 2024 ). The SNPs (Single Nucleotide Polymorphisms) are one of the main genetic variations in miRNA-coding regions, which can affect several processes such as transcription, maturation, and miRNA–mRNA interactions. Evidence has shown that SNPs in miRNAs may influence the miRNAs’ expression levels and eventually alter their functions on targets (Parchami et al. 2017 ). Among the principal SNPs in the miRNAs of interest is miRNA-27a rs895819 T>C (A>G in reverse orientation to the genome), located on 19p13.12, in the loop of pre-miR-27. The change of A to G may modify its secondary structure, with alterations in the expression of its target gene and the miRNA function (Xu et al. 2013 ). Cancer promotion or tumor suppression has already shown an association with endometriosis (Jaafar et al. 2022 ), endometrial cancer (Ghazala et al. 2021 ), and recurrent pregnancy loss (Shaker et al. 2020 ). Additionally, miRNA-222 rs2858060 G>C, located on Xp11.3, is probably situated in the binding site of the transcription factor, and could influence the production of miR-222 and the binding of a transcription factor. This polymorphism has been associated with the risk of Polycystic Ovary Syndrome (PCOS) (Hosseini et al. 2017 , Long et al. 2014 , Yang et al. 2021 ) and was found to be involved in apoptosis, cell cycle, and endocrine pathways, such as MAPK, Wnt, and Jak-STAT signaling pathways (Long et al. 2014 ). The miRNA-499a rs3746444 A>G polymorphism is located on 20q11.22, in the stem region opposite to the mature miR-499 sequence, and results in a change in the stem structure of miR-499. Compared with the A allele, the secondary structure for the G allele is less stable (Fan et al. 2013), and this polymorphism has already been associated with endometriosis (Farsimadan et al. 2021 ), endometrial cancer prognosis (Wu et al. 2019 ), cervical cancer (Wang et al. 2019 ), PCOS (Li et al. 2022 ), and recurrent miscarriage (Parveen & Agrawal 2015 ). However, further research is needed on these three polymorphisms in endometriosis. Therefore, this study aimed to determine the allelic and genotypic frequencies of the rs895819, rs2858060, and rs3746444 polymorphisms and their possible association with endometriosis. MATERIALS AND METHODS This case-control study, was approved by the Research Ethics Committee of the Federal University of Triângulo Mineiro (UFTM) under Protocol N°1628. Informed consent was obtained from all individual participants included in the study. Casuistry consisted of 143 women treated at the UFTM Outpatient Gynecology and Obstetrics Clinic; 54 had endometriosis (case group) and 89 had no endometriosis (control group). The criteria adopted for the diagnosis were performing a videolaparoscopy to confirm (cases) or exclude (controls) endometriosis. Peripheral blood samples were employed for extracting genomic DNA, and the salting-out procedure was used (Miller et al. 1988 ). Electrophoresis in agarose gel 1% was conducted to verify the quality of samples, followed by spectrophotometry to quantify DNA concentration. The ratio of the A260/A280 readings was approximately 1.8 for most samples at the NanoDropTM 2000. All polymorphisms from miRNA-27a, miRNA-222, and miRNA-499a were analyzed by real-time Polymerase Chain Reaction (PCR) using the StepOnePlus™ System and TaqMan Assays. Figure 1 shows the probes used and the number of samples with success in the real-time PCR reaction for each polymorphism investigated. The number of genotyped samples varied across three SNPs due to failed reactions. Figure 1 Flowchart of each polymorphism investigated, and its respective TaqMan Assays by Thermofisher, in cases (ED) and controls (C). All the real-time PCR was performed using a negative control. The amplification conditions were denaturation at 95°C for 10 minutes, followed by 50 cycles of denaturation at 95°C for 15 seconds, annealing for 1 minute at 60°C, and extension for 30 seconds at 60°C. After the cycles, the final extension was performed at 60°C for 30 seconds. All experiments were made to be duplicated, and genotyping was conducted by manual inspection of allele discrimination plots (fluorescence clusters). For the statistical analysis, the chi-square test and exact Fisher’s test were used to analyze the genotypic and allelic distribution of the polymorphisms and estimate the Hardy-Weinberg Equilibrium (HWE). The SNPStats program (available at <http://bioinfo.iconcologia.net/SNPstats_web>) was employed for the logistic regression model adjusted for age and to evaluate the association between polymorphisms and the development of endometriosis. The following models assessed the effect of polymorphisms: 1-Codominance (wild-type homozygote x heterozygous x polymorphic homozygote); 2-Dominance (wild-type homozygous x heterozygous + polymorphic homozygous); 3-Recessive (polymorphic homozygote x wild-type homozygote + heterozygous). However, we should underscore that not all individuals were subjected to this investigation due to a lack of some data. The results were presented in odds ratio (OR) and 95% confidence interval (CI - 95%). The level of statistical significance was defined as p<0.05 for all analyses. RESULTS The results of allelic and genotyping frequencies of three polymorphisms are shown in Table I . No significant differences in the genotype frequencies were found at miRNA-27a rs895819 between groups (χ2 = 2.57; p = 0.27). Regarding the miRNA-222 rs2858060 polymorphism, the genotype frequencies showed a difference between cases and controls (χ2 = 8.42; p = 0.01). However, the miRNA-499a rs3746444 showed no difference between the studied populations (χ2 = 3.65; p = 0.16). No statistical difference was recognized between groups for allelic frequencies (p = 1.00, p = 0.22, and p = 1.00, respectively). The discrepancies regarding the number of cases and controls shown in Table I are due to non-real-time amplification of some samples. Thumbnail Table I Frequency distribution of miRNA-27a rs895819, miRNA-222 rs2858060, and miRNA-449a rs3746444 genotypes and alleles in endometriosis patients and controls. The genotypes frequencies in miRNA-27a rs895819 polymorphism are in HWE (cases: χ 2 = 0.35; p = 0.56; controls: χ 2 = 3.36; p = 0.07). Regarding the miRNA-222 rs2858060 polymorphism, the genotype frequencies are in HWE to the cases (χ 2 = 0.09; p = 0.50), but the control group was in disequilibrium (χ 2 = 11.14; p<0.05). Regarding the miRNA-499a polymorphism, the genotype frequencies are in HWE to the cases (χ 2 = 0.08; p = 0.77), but the control group was in disequilibrium (χ 2 = 6.58; p=0.01). Table II shows the association analysis of the polymorphisms evaluated in this study. The analysis for rs895819 and rs3746444 polymorphisms did not reveal a statistical difference between the groups for the models. The rs2858060 had a statistical difference between the groups for the recessive model (OR = 3.68, 95% CI: 0.94-14.39, p = 0.04), with a higher frequency of recessive homozygotes in the control group. Thumbnail Table II Association of codominant, dominant, and recessive of miRNA-27a (n=112, 43 cases and 69 controls), miRNA222 (n=93, 45 cases and 48 controls), and miRNA499a (n=104, 42 cases and 62 controls) genotypes in endometriosis patients and controls. DISCUSSION The literature reports a significant role of miRNAs in endometriosis development (Monnaka et al. 2021 , Soltani-Fard et al. 2023 , Begum et al. 2023 ). Our research group previously studied the polymorphisms rs2910164 miR-146a and rs11614913 miR-196a2 in endometriosis, but these two polymorphisms were not associated with endometriosis in the studied population (Oliveira et al. 2024 ). Notably, the availability of miRNAs as biomarkers in several biological fluids, such as blood, urine, and menstrual fluid, has made them a promising candidate for developing a “signature of miRNAs” for the diagnosis of endometriosis (Encalada Soto 2024). MiRNAs regulate several genes involved in endometriosis. Among the most prominent are ERα/β, KRAS4A/4B, CYP19, IL-6, HOXA9, HOXA10, and EDN1 – all relevant to disease pathophysiology. The miRNAs further modulate mTOR signaling and the VEGF pathway, affecting cell growth, migration, and angiogenesis – principal mechanisms in lesion development. A systematic review published recently included 17 studies examining miRNAs in women with endometriosis compared to controls. The authors concluded that the findings were encouraging, and if validated, miRNAs may offer a transformative, non-invasive approach for earlier detection and improved management of endometriosis (Dryja-Brodowska et al. 2025 ). A recent systematic review of the literature investigated the expression of miRNAs in the endometrium and their potential regulatory roles under pathological conditions, including endometriosis. A list of miRNAs with decreased and increased expression is presented, considering their role in the pathogenesis of the most noticeable endometrial diseases (Kluz et al. 2024 ). The present study investigated three other polymorphisms: miRNA-27a rs895819, miRNA-222 rs2858060, and miRNA-499a rs3746444. However, only the second one was linked to pathology. These same polymorphisms were investigated in other gynecological conditions, and the results are shown in Table III . Five studies were published on the miRNA-27a rs898519 polymorphism, one of them in endometriosis (Jaafar et al. 2022 ), only two for miRNA-222 rs2858060, and three for the last polymorphism, one of which is also investigated in patients with endometriosis (Farsimadan et al. 2021 ) (Table III). Thumbnail Table III Summary of the main findings from previous studies investigating rs895819, rs2858060, and rs3746444 polymorphisms in female reproductive disorders. The data in Table III show a predominance of studies conducted in China (n=3) and Iran (n=3). These data are in agreement with a previous review on miRNAs in endometriosis that showed predominance of research conducted in Asia (n=7), particularly in countries such as China, Korea, Iran, and Iraq (Dryja-Brodowska et al. 2025 ). Both studies were conducted in close geographic regions and in populations with well-defined ethnicity; so, they do not report the genetic diversity of the world population. Our findings are inconsistent with those presented by a prior study (Jaafar et al. 2022 ), which showed that rs895819 was significantly associated with endometriosis under the dominant, recessive, codominant, and allelic models. Also, it had a protective effect on endometriosis severity for AG genotype and G allele in rs895819, and they concluded that miR-27a rs895819 is linked to endometriosis. Other gynecological conditions have previously been linked to this polymorphism, such as PCOS (Mir et al. 2022), cervical cancer (Chen et al. 2020 ), idiopathic recurrent pregnancy loss (Rah et al. 2017 ), and recurrent spontaneous abortion (Wang et al. 2016 ). These discrepant results may be because patients in other studies were from different continents, particularly Asia (Table III), and were probably influenced by the ethnicity and genetic background of the population (Colucci et al. 2022 ). Given that miRNA expression can be influenced by genetic, environmental, and lifestyle factors, the inclusion of multi-ethnic cohorts is essential to ensure broader applicability and generalizability of findings (Dryja-Brodowska et al. 2025 ). The rs2858060 of miRNA-222 was not found in a previous study regarding its association with endometriosis, although previous research had observed a different expression of this molecule in ovarian endometriomas when compared with the eutopic endometrium (Ramón et al. 2011 ). This study aimed to analyze several miRNAs related to angiogenesis, so they used TaqMan real-time PCR to assess the expression of some miRNAs, among them miRNA-222, and investigated 58 women with endometriosis and 38 controls (Ramón et al. 2011 ). The results displayed in Table III show that the two studies published in the literature on this polymorphism are discordant (Hosseini et al. 2017 , Yang et al. 2021 ). However, our study identified a significant association of miRNA-222 rs2858060 with endometriosis, including the recessive inheritance model, and further studies are required for confirmation. A higher frequency of the GG genotype was observed in the controls; consequently, women carrying the GG genotype are more likely to not develop endometriosis than women carrying the CG and CC genotypes. To date, there is no study regarding the effect of the rs2858060 polymorphism in the pathogenesis of endometriosis; therefore, the present study was the first to assess this association. Our results concerning the rs3746444 polymorphism of miRNA-499a did not reveal a difference between the case and control groups. In the present study, no relationship was observed between rs3746444 and endometriosis in the inheritance models analyzed. Nevertheless, this polymorphism showed a borderline association with endometriosis under the recessive model (p=0.05) (Farsimadan et al. 2021 ). It is also related to other gynecological conditions, such as PCOS, where it was linked to the disease in the allelic, dominant, and recessive models in a case-control study (Li et al. 2022 ) and with recurrent pregnancy loss (Parveen & Agrawal 2015 ). The miRNA-222 (rs2858060) and miRNA-499a (rs3746444) polymorphisms were in disequilibrium in the controls, suggesting that some evolutionary force is acting on this population. The leading causes of Hardy-Weinberg disequilibrium in controls can be the selection bias or genotyping error (in this study, each sample was analyzed in duplicate to confirm the genotype). A competing risk of disease occurrence associated with the polymorphic allele could be an explanation for this disequilibrium and lack of association. It should also be noted that population selection and stratification or the study sampling plan are delicate issues that could be the cause of Hardy-Weinberg disequilibrium (Yu et al. 2009 ). The rs2858060 showed a significant difference between the genotype frequencies in the studied population, with an increased frequency of the GG genotype in the controls, but for rs3746444 a result like that was not observed. Therefore, can be suggested a positive evolutionary force acting on the G allele of the polymorphism miRNA-222 rs2858060 in this study population. Although the data found is highly valuable to the scientific community, this study has limitations, such as the small sample size compared to other research. Additionally, we underscore that a study should include diverse ethnic groups and different regions to mitigate these limitations, as we observed how this can influence the outcomes. In addition, it is important to analyze the molecular concentration of these biomarkers in other compartments, since it is established in the literature that we already know that miRNA is differentially expressed in fluids and endometrial tissue, suggesting gene regulation (Begum et al. 2023 ). However, a strength of this work is that the investigation of these three specific miRNA polymorphisms in endometriosis is a research area that remains underexplored in the Brazilian population. In addition, the analysis of the rs2858060 polymorphism in miRNA-222 in this study is unpublished. CONCLUSIONS The present study shows that the rs895819 polymorphism of miRNA-27a and the rs3746444 miRNA-499a are not associated with endometriosis, while the miRNA-222 rs2858060 displays a preliminary and exploratory indication of association. This work represents an advance in endometriosis genetics since it reveals a link between endometriosis and miRNA variants. Studies with a larger sample size are needed to validate our results, as they allow for greater robustness in findings. Acknowledgements The authors would like to thank FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais) (Grant number APQ-01545-21) for their financial support and scientific initiation fellowship to JAB. Data availability All data generated or analyzed during this research are included in this published article. References BEGUM MIA, CHUAN L, HONG ST & CHAE HS. 2023. The Pathological Role of miRNAs in Endometriosis. Biomedicines 11(11): 3087. BERNARDI JA, CINTRA MTR & MARQUI ABT. 2024. 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Edited by Handling editor Guilherme Baldo Data availability All data generated or analyzed during this research are included in this published article. Publication Dates Publication in this collection 03 Aug 2026 Date of issue 2026 History Received 20 Dec 2024 Accepted 24 Jan 2026 This is an open-access article distributed under the terms of the Creative Commons Attribution License Authorship .author-card { border-bottom: 1px solid #ccc; padding: 1rem 0; } .author-card:last-child { border-bottom: 0px; } .author-name { font-weight: 600; } .orcid-button { padding-left: 2.5rem; } .modal-body { padding-bottom: 3rem; } .orcid-button::before { content: \"\"; position: absolute; background-image: url(https://ds.scielo.org/img/logo-orcid.svg); background-repeat: no-repeat; background-size: 1.5em auto; background-position: .5em center; display: block; width: 60px; height: 60px; top: -10px; left: 0; } person JÚLIA A. BERNARDI Project development · Data Collection · Data analysis and Manuscript writing/editing. school Universidade Federal do Triângulo Mineiro (UFTM), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil 0009-0001-7124-9845 person MARIANGELA T.R. CINTRA Protocol/project development · Data collection or management · Data analysis · Manuscript writing/editing · Supervision and Funding acquisition. school Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Exatas, Naturais e Educação (ICENE), Departamento de Ciências Biológicas, Av. Randolfo Borges Júnior, 1400, Univerdecidade, 38064-200 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Exatas, Naturais e Educação (ICENE), Departamento de Ciências Biológicas, Av. Randolfo Borges Júnior, 1400, Univerdecidade, 38064-200 Uberaba, MG, Brazil 0000-0002-8223-805X person MARCO F.P. LIMA Data collection and Data analysis. school Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil 0000-0001-7271-6620 person MARIANA K.O. GOMES Data collection and Data analysis. school Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil 0000-0002-5279-5242 person ALESSANDRA B.T. DE MARQUI Protocol/project development · Data collection or management · Data analysis · Manuscript writing/editing · Supervision and Funding acquisition. school Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Biológicas e Naturais (ICBN), Departamento de Patologia, Genética e Evolução (DPGE), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Biológicas e Naturais (ICBN), Departamento de Patologia, Genética e Evolução (DPGE), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil 0000-0003-2361-5174 Correspondence to: Alessandra Bernadete Trovó de Marqui email alessandra.marqui@uftm.edu.br Handling editor Guilherme Baldo SCIMAGO INSTITUTIONS RANKINGS Universidade Federal do Triângulo Mineiro (UFTM), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Exatas, Naturais e Educação (ICENE), Departamento de Ciências Biológicas, Av. Randolfo Borges Júnior, 1400, Univerdecidade, 38064-200 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Exatas, Naturais e Educação (ICENE), Departamento de Ciências Biológicas, Av. Randolfo Borges Júnior, 1400, Univerdecidade, 38064-200 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências da Saúde (ICS), Departamento de Ginecologia e Obstetrícia (DGO), Av. Getúlio Guaritá, 214, 38025-440 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Biológicas e Naturais (ICBN), Departamento de Patologia, Genética e Evolução (DPGE), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM) Brazil Uberaba, MG, Brazil Universidade Federal do Triângulo Mineiro (UFTM), Instituto de Ciências Biológicas e Naturais (ICBN), Departamento de Patologia, Genética e Evolução (DPGE), Disciplina de Genética, Campus I, Praça Manoel Terra, 330, Nossa Senhora da Abadia, 38025-015 Uberaba, MG, Brazil Figures | Tables Figures (1) Tables (3) Thumbnail Figure 1 Flowchart of each polymorphism investigated, and its respective TaqMan Assays by Thermofisher, in cases (ED) and controls (C). Thumbnail Table I Frequency distribution of miRNA-27a rs895819, miRNA-222 rs2858060, and miRNA-449a rs3746444 genotypes and alleles in endometriosis patients and controls. Thumbnail Table II Association of codominant, dominant, and recessive of miRNA-27a (n=112, 43 cases and 69 controls), miRNA222 (n=93, 45 cases and 48 controls), and miRNA499a (n=104, 42 cases and 62 controls) genotypes in endometriosis patients and controls. Thumbnail Table III Summary of the main findings from previous studies investigating rs895819, rs2858060, and rs3746444 polymorphisms in female reproductive disorders. image Figure 1 Flowchart of each polymorphism investigated, and its respective TaqMan Assays by Thermofisher, in cases (ED) and controls (C). open_in_new table_chart Table I Frequency distribution of miRNA-27a rs895819, miRNA-222 rs2858060, and miRNA-449a rs3746444 genotypes and alleles in endometriosis patients and controls. rs 895819 polymorphism T>C Cases (n=50) Controls (n=77) p Genotypes n (%) n (%) 0.27 CC 9 (18) 9 (11.7) CT 22 (44) 45 (58.4) TT 19 (38) 23 (29.9) Alleles 1.00 C 0.40 0.41 T 0.60 0.59 rs 2858060 polymorphism G>C Cases (n=53) Controls (n=55) p Genotypes n (%) n (%) 0.01 CC 27 (50.9) 28 (50.9) CG 23 (43.4) 14 (25.5) GG 3 (5.7) 13 (23.6) Alleles 0.22 C 0.73 0.64 G 0.27 0.36 rs 3746444 polymorphism A>G Cases (n=48) Controls (n=67) p Genotypes n (%) n (%) 0.16 AA 11 (22.9) 22 (32.8) AG 25 (52.1) 23 (34.4) GG 12 (25.0) 22 (32.8) Alleles 1.00 A 0.49 0.50 G 0.51 0.50 table_chart Table II Association of codominant, dominant, and recessive of miRNA-27a (n=112, 43 cases and 69 controls), miRNA222 (n=93, 45 cases and 48 controls), and miRNA499a (n=104, 42 cases and 62 controls) genotypes in endometriosis patients and controls. SNP Model Cases Controls OR (95% CI) p-value rs895819 Codominant T/T C/T C/C 17 (39.5%) 18 (41.9%) 8 (18.6%) 19 (27.5%) 42 (60.9%) 8 (11.6%) 1.00 2.09 (0.89-4.91) 0.89 (0.28-2.91) 0.14 Dominant T/T C/T – C/C 17 (39.5%) 26 (60.5%) 19 (27.5%) 50 (72.5%) 1.00 1.72 (0.77-3.86) 0.19 Recessive T/T – C/T CC 35 (81.4%) 8 (18.6%) 61 (88.4%) 8 (11.6%) 1.00 0.57 (0.20-1.66) 0.31 rs2858060 Codominant C/C C/G G/G 22 (48.9%) 20 (44.4%) 3 (6.7%) 25 (52.1%) 13 (27.1%) 10 (20.8%) 1.00 0.57 (0.23-1.41) 2.93 (0.71-12.04) 0.06 Dominant CC C/G – G/G 22 (48.9%) 23 (51.1%) 25 (52.1%) 23 (47.9%) 1.00 0.88 (0.39-1.99) 0.76 Recessive C/C – C/G G/G 42 (93.3%) 3 (6.7%) 38 (79.2%) 10 (20.8%) 1.00 3.68 (0.94-14.39) 0.04 rs3746444 Codominant G/G A/G A/A 9 (21.4%) 23 (54.8%) 10 (23.8%) 22 (35.5%) 21 (33.9%) 19 (30.6%) 1.00 0.37 (0.14-0.99) 0.78 (0.26-2.31) 0.10 Dominant G/G A/G – A/A 9 (21.4%) 33 (78.6%) 22 (35.5%) 40 (64.5%) 1.00 0.50 (0.20-1.22) 0.12 Recessive G/G – A/G A/A 32 (76.2%) 10 (23.8%) 43 (69.3%) 19 (30.6%) 1.00 1.41 (0.58-3.45) 0.44 table_chart Table III Summary of the main findings from previous studies investigating rs895819, rs2858060, and rs3746444 polymorphisms in female reproductive disorders. Study Country Objective(s) Subjects Gynecological condition analyzed Polymorphism Association with the gynecological condition analyzed Jaafar et al. 2022 Iraq Evaluated the prevalence and the association of three different miRNAs variants including, miR-27a rs895819, miR-124-1 rs531564, and miR-423 rs6505162 with endometriosis 220 cases and 220 controls Endometriosis miRNA-27a rs898519 miRNA-27a: yes Wang et al. 2016 China Investigate the possible associations of miRNA-27a and Leptin polymorphisms with the risk of spontaneous abortion 138 cases and 142 controls Recurrent spontaneous abortion miRNA-27a rs898519 miRNA-27a: yes Chen et al. 2020 China Identify common genetic polymorphisms of pre-miRNAs associated with the risk of cervical cancer susceptibility 290 cases and 445 controls Cervical cancer Pre-miRNA-27a rs898519 miRNA-27a: yes (protective effects) Rah et al. 2017 South Korea Investigate whether genetic polymorphisms in the four miRNAs associated with fetal or placental development play roles in the development of idiopathic recurrent pregnancy loss. 387 cases and 225 controls Idiopathic recurrent pregnancy loss miRNA-27a rs898519 miRNA-27a: yes Mir et al. 2022 Saudi Arabia Characterize the biochemical and endocrine parameters in polycystic ovary syndrome and the influence of allelic variations in the genes of miRNAs 27a (rs895819), 196a2 (rs11614913), 423 (rs6505162), and in the transcription factor KLF14 gene polymorphism (rs972283) on the risk and susceptibility to the disease 115 cases and 115 controls Polycystic ovary syndrome miRNA-27a rs898519 miRNA-27a: yes Hosseini et al. 2017 Iran Investigate the association of microRNA-146a (rs2910164) and microRNA-222 (rs2858060) polymorphisms with susceptibility to polycystic ovary syndrome 205 cases and 205 controls Polycystic ovary syndrome miRNA-222 rs2858060 miRNA-222: yes Yang et al. 2021 China Investigate the association of polymorphisms rs1292037, rs13137 in miR-21; rs2227255, rs2227258 in miR-26b; rs2858061, rs34678647, rs2858060, rs2745709 in miR-221/222; rs2297537, rs2297538 in miR-126 with cervical intraepithelial neoplasia and cervical cancer 435 cases of cervical intraepithelial neoplasia, 743 cases of cervical cancer and 998 controls Cervical intraepithelial neoplasia and cervical cancer miRNA-222 rs2858060 miRNA-222: no Farsimadan et al. 2021 Iran Evaluated the prevalence of miRNAs variants miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 in endometriosis 260 cases and 260 controls Endometriosis miRNA-449a rs3746444 miRNA-499a: yes Li et al. 2022 Iran Clarify the significance of four miRNA variants miR-126 rs4636297, miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444 and PCOS 385 cases and 385 controls Polycystic ovary syndrome miRNA-449a rs3746444 miRNA-499a: yes Parveen & Agrawal 2015 India Investigate the role of miR-146aC > G (rs2910164), miR-149T > C (rs2292832), miR-196a2T > C (rs11614913), and miR-499A > G (rs3746444) gene polymorphisms in miscarriages 200 cases and 300 controls Recurrent miscarriage miRNA-449a rs3746444 miRNA-499a: yes How to cite link copy function currentDate() { var today = new Date(); var months = ['January', 'February', 'March', 'April', 'May', 'June', 'July', 'August', 'September', 'October', 'November', 'December'] today.setTime(today.getTime()); return today.getDate() + \" \" + months[today.getMonth()] + \" \" + today.getFullYear(); } var citation = 'BERNARDI, JÚLIA A. et al. Investigation of the miRNA27a rs895819, miRNA222 rs2858060 and miRNA499a rs3746444 polymorphisms in Endometriosis. Anais da Academia Brasileira de Ciências [online]. 2026, v. 98, suppl 1 [Accessed CURRENTDATE], e20241498. Available from: <https://doi.org/10.1590/0001-3765202620241498>. Epub 03 Aug 2026. 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