Study on correlation between gene polymorphism of PDE5 rs3806808 locus and erectile dysfunction

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Nevertheless, the impact of phosphodiesterase 5 ( PDE5 ) gene mutations on the susceptibility to ED remained uncertain. For this study, 627 patients were enrolled and evaluated for ED by utilizing the International Index of Erectile Function-5. The PDE5 mutation was analyzed through fluorescence-based polymerase chain reaction (PCR). There were no notable variations among the genotypic distribution of the PDE5 gene polymorphism (TT, GT, and GG) at rs3806808 locus observed between individuals in the non-ED and ED cohorts. Furthermore, in both crude and adjusted binary logistic regression models, the presence of the PDE5 gene polymorphism did not demonstrate a significant association with the risk of ED. Interestingly, a significantly higher prevalence of the PDE5 TT polymorphism at the rs3806808 locus was detected in cases of moderate and severe ED ( P = 0.01). The link between the PDE5 TT polymorphism and severe ED was supported by logistic regression analysis, even after considering potential confounding factors (odds ratio [OR] = 2.35, 95% confidence interval [CI]: 1.04–5.39, P = 0.01). The study findings suggested a direct link between the presence of the PDE5 TT polymorphism and a heightened risk of severe ED. Identification of PDE5 gene polymorphisms could offer additional insights for clinicians in the routine diagnosis of patients with ED. Erectile dysfunction (ED) PDE5 gene polymorphism rs3806808 locus Genetic susceptibility Severe ED risk INTRODUCTION The condition of erectile dysfunction (ED) was defined by the difficulty in attaining or sustaining an erection suitable for fulfilling sexual activity ( 1 ). Among adult males, ED was a prevalent issue, affecting approximately 12–19% of individuals within the reproductive age group ( 2 ). Various underlying mechanisms contribute to ED, including vascular, neurogenic, and psychogenic factors, with vascular causes being the most prevalent( 3 ). Factors related to lifestyle and conditions like diabetes, hypertension, and dyslipidemia were significant factors contributing to vascular ED ( 4 ). The reduced function of the nitric oxide (NO)-dependent relaxation system was a primary cause of ED ( 5 ). Upon sexual stimulation, the activation of the constitutive nitric oxide synthase (NOS3) enzyme in the endothelial cells was sustained due to the blood vessels and sinusoidal pressures exerted on them. NO triggered the activation of soluble guanylate cyclase (sGC) and promotes the production of cyclic guanosine monophosphate (cGMP) ( 6 ). Phosphodiesterase 5 ( PDE5 ) was responsible for the breakdown and elimination of cGMP. Research had demonstrated the significant involvement of PDE5 in the progression of ED. PDE5 inhibitors could reduce the hydrolysis of cGMP and prolong the relaxation time of penile blood vessels and corpus cavernosum smooth muscle, effectively maintaining penile erection( 7 – 9 ). PDE5 inhibitors, represented by sildenafil, had shown great efficacy in treating ED, but there were also some patients with poor response, which might be due to the polymorphism of the PDE5 coding gene. Researches had shown that polymorphism of the PDE5 at rs3806808 locus was an important factor affecting the efficacy of sildenafil( 10 ). However, there were currently few studies on the relationship between PDE5 gene polymorphism with rs3806808 mutation and ED. This study analyzes the relationship between PDE5 gene polymorphism at rs3806808 locus and the onset of ED. PARTICIPANTS AND METHODS Participants 627 individuals from the andrology department undergoing fertility assessment at The First Affiliated Hospital of Shandong Second Medical University in China (Shandong, China) between May 2023 and March 2024 were enrolled in this cross-sectional investigation. Included in this study were participants who completed the survey. Exclusion criteria consisted of: (1) males aged 50 years or older; (2) males with hypertension, high cholesterol, or diabetes; or (3) males with a prior history of urinary or genital infections and varicocele. An andrologist conducted physical examinations on all participants. Approval for the research was obtained from the Ethics Committee at the First Affiliated Hospital of Shandong Second Medical University of China (Approval No. 20220521-JY-001). The study was conducted in accordance with the Declaration of Helsinki and its later amendments. All individuals were asked to provide written informed consent before participating in the study. Questionnaires administration and ED evaluation A comprehensive questionnaire covering various aspects was completed by the participants in this study. These included demographic characteristics such as age, weight, height, educational level, and infertility time. Factors related to lifestyle such as smoking and drinking habits were also assessed. Furthermore, participants provided information on their medical history, including conditions like hypertension, diabetes, hyperlipidemia, varicoceles, cryptorchidism, and testicular cancer. To assess erectile function, the Chinese version of the International Index of Erectile Function-5 (IIEF-5) questionnaire was utilized. The focus of the IIEF-5 questionnaire includes parameters such as confidence in attaining and sustaining an erection, rigidity of erections, ability to maintain an erection during sexual intercourse, frequency of maintaining erections, and satisfaction with sexual intercourse. The total score on the questionnaire ranged from 1 to 25. Each participant completed the IIEF-5 questionnaire independently to minimize any potential influence came from the doctors. ED was classified based on the IIEF-5 score as follows: no symptoms (score 22-25), mild symptoms (score 17-21), moderate symptoms (score 12-16), and severe symptoms (score 1-11). Measurements of the PDE5 G>T variant at rs3806808 locus At the commencement of the study, all participants were asked to undergo a blood sample collection by venipuncture. The collected samples were utilized for the extraction of total genomic DNA utilizing the QIAamp DNA Mini Kit (Qiagen, Hilden, Germany). Detection of the PDE5 rs3806808 G>T variant was carried out using fluorescence polymerase chain reaction (PCR) following the protocol provided by the manufacturer (Talde Medical Group, Shenzhen, China). Statistical analyses The body mass index (BMI) was calculated by dividing the weight in kilograms by the square of the height in meters. The participants were categorized into two groups based on their IIEF-5 scores: the ED group and the non-ED group. Frequencies were used to represent qualitative variables, whereas mean ± standard deviation (s.d.) was employed to report quantitative variables. Student's t-test was used to compare parametric continuous data, while Pearson's chi-squared test was employed to analyze categorical data. To evaluate the relationship between ED and the PDE5 gene polymorphism, logistic regression analysis was conducted. Two models were employed: a crude model and an adjusted model. The adjusted model incorporated covariates such as age, BMI, smoking, drinking, education level, and infertility time. Statistical analyses were carried out using GraphPad Prism 9.0 software (GraphPad Software, San Diego, CA, USA). The significance level was set at a P -value of less than 0.05. RESULTS A total of 627 male participants (mean [s.d.] age: 29.8 [3.3] years) were enrolled in this research ( Table 1 ). The participants were divided into two groups based on their IIEF-5 score: the non-ED group ( n = 258) and the ED group ( n = 369). The age comparison between the non-ED group (mean [s.d.] age: 29.9 [3.2] years; P = 0.71) and the ED group (mean [s.d.] age: 29.8 [3.4] years) did not reveal any significant differences. Furthermore, the non-ED group exhibited a slightly higher BMI, although this disparity was not deemed statistically significant. The two groups showed comparable Factors related to lifestyle, such as tobacco use and alcohol consumption. Notably, the non-ED group exhibited a notably higher education level ( P < 0.001), which aligns with the results of a previous study (11). Moreover, there were no significant disparities noted in the genotypic frequencies of the PDE5 rs3806808 polymorphism (TT, GT, and GG) between non-ED groups and the ED group ( P = 0.26). Studies had reported variations in enzyme activity levels amongst the different PDE5 rs3806808 polymorphisms, Moreover, our findings further corroborated individuals with the PDE5 TT gene type had higher levels of serum cGMP than men with the PDE5 GT and GG gene types ( Table 2 ). Despite having a relatively high number of cases, our participants exhibited a lower prevalence of the PDE5 T allele compared to the prior study(12) ( Table 3 ). Table 4 displayed a summary of the demographic characteristics of participants, categorized according to their PDE5 gene polymorphisms, is presented. The results of a binary logistic regression analysis, investigating the correlation between ED and variables such as education level, infertility time, and the PDE5 gene polymorphism, were presented in Table 5 . Compared to the reference group (university), men with a lower education level (primary school, junior high school, and high school) exhibited an increased risk of ED (odds ratio [OR] = 25.68; P = 0.001, OR = 1.88, P < 0.001; OR = 1.79, P < 0.001, respectively). Conversely, no significant correlation was found between ED and infertility time ( P = 0.15). Both crude and adjusted models indicated that the PDE5 gene polymorphism was not significantly linked to the risk of ED (crude, GG vs GT [ P = 0.07], GG vs TT [ P = 0.12]; adjusted, GG vs GT [ P = 0.15], GG vs TT [ P = 0.18]). Further explorations were carried out to examine the association between the distribution of PDE5 gene polymorphisms and the severity of ED, as determined by the categorizations of the IIEF-5 scores (1-11: severe, 12-16: moderate, 17-21: mild). In individuals with severe and moderate ED, there was a notably higher frequency of homozygous TT polymorphism ( P = 0.01; Table 6 ). However, there was no significant difference in the severity of ED between men with PDE5 GT ( P = 0.09) and TT polymorphisms ( P = 0.26). After adjusting for potential confounding variables, logistic regression analysis demonstrated a significant positive association between the PDE5 TT polymorphism and severe ED (crude OR = 2.44, 95% CI: 1.10-5.45, P = 0.01; adjusted OR = 2.35, 95% CI: 1.04-5.39, P = 0.01; Table 7 ). Table 1: Demographic characteristics of the study population Demographic characteristic Total individuals (n=627) ED group (n=369) Non-ED group (n=258) P Age(year), mean±s.d. 29.8±3.3 29.8±3.4 29.9±3.2 0.71 Age (year), n (%) 0.99 <30 250 (39.9) 142 (38.5) 108 (41.5) 30-39 344 (54.9) 205 (55.6) 139 (53.9) ≥40 33 (5.3) 22 (6.0) 11 (4.7) BMI (kg·m -2 ), mean±s.d. 23.5±4.7 23.3±4.9 23.7±4.5 0.30 Alcohol amount, n (%) 0.87 Nondrinking 290 (46.3) 172 (46.6) 117 (45.7) Drinking 337 (53.7) 197 (53.4) 140 (54.3) Smoking amount, n (%) 0.27 Nonsmoking 347 (55.4) 200 (54.2) 147 (57.2) Smoking 280 (44.6) 169 (45.8) 111 (42.8) Education level, n (%) <0.001 Primary school 15 (2.4) 14 (3.9) 1 (0.2) Junior high school 137 (21.9) 95 (25.8) 42 (17.4) High school 108 (17.2) 72 (19.5) 36 (14.2) University 367 (58.5) 188 (51.0) 179 (68.2) Infertility time, n (%) 0.37 3 years 75 (12.0) 47 (12.6) 29 (11.0) PDE5 gene polymorphism, n (%) 0.26 GG 186 (29.7) 102 (27.7) 84 (32.6) GT 301 (48.0) 182 (49.3) 119 (46.1) TT 140 (22.3) 85 (23.0) 55 (21.3) IIEF-5 score, median (IQR) 20 (17-24) 17 (15-21) 24 (22-25) <0.001 P values were assessed using Pearson's Chi-square test and Student's t -test. s.d.: standard deviation; IQR: interquartile range; ED: erectile dysfunction; BMI: body mass index; IIEF-5: International Index of Erectile Function-5; PDE5 : phosphodiesterase 5; GG signifies the PDE5 GG polymorphism, GT represents the PDE5 GT polymorphism, and TT denotes the PDE5 TT polymorphism. Table 2: Cyclic guanosine monophosphate levels in participants based on the phosphodiesterase 5 rs3806808 polymorphism Variable PDE5 rs3806808 polymorphism P 1 P 2 P 3 GG (n=4) GT (n=8) TT (n=6) cGMP (μmol -1 ) 19.5±2.3 19.0±1.5 25.6±2.3 0.99 0.0006 <0.0001 P 1 , GG VS GT; P 2 , GG VS TT; P 3 , GT VS TT. PDE5 : phosphodiesterase 5; cGMP: cyclic guanosine monophosphate; GG: PDE5 GG polymorphism; GT: PDE5 GT polymorphism; TT: PDE5 TT polymorphism. Table 3: Comparing the distribution of phosphodiesterase 5 polymorphism between our study population and a previous study of general men PDE5 gene polymorphisms Our study, n (%) Prior study, n (%) P GG 186(29.7) 12 (14.4) <0.001 GT 301(48.0) 39 (47.0) TT 140(22.3) 32 (38.6) Allele G 673(53.7) 32 (37.9) <0.001 Allele T 581(46.3) 51 (62.1) PDE5 : phosphodiesterase 5; GT: PDE5 GT polymorphism; TT: PDE5 TT polymorphism; GG: PDE5 GG polymorphism; Table 4: Demographic Profile of Participants Based on Phosphodiesterase 5 Polymorphism. Clinical characteristic GG (n=186) GT (n=301) TT (n=140) P Age (year), mean±s.d. 29.9±3.0 29.8±3.4 30.0±3.6 0.97 BMI (kg·m -2 ), mean±s.d. 23.2±4.6 23.7±4.9 23.5±4.5 0.26 Alcohol amount, n (%) 0.56 Nondrinking 89 (47.8) 140 (46.5) 118 (43.6) Drinking 97 (52.2) 161 (53.5) 79 (56.4) Smoking amount, n (%) 0.32 Nonsmoking 99 (53.2) 173 (57.5) 76 (54.3) Smoking 87 (46.8) 128 (42.5) 64 (45.7) Education level, n (%) 0.26 Primary school 3 (1.6) 9 (3.0) 2 (1.4) Junior high school 35 (18.8) 70 (23.3) 33 (23.6) High school 33 (17.7) 49 (16.2) 26 (18.6) university 115 (58.5) 173 (57.5) 79 (56.4) Infertility time, n (%) 0.86 3 years 23 (12.4) 35 (11.6) 18 (12.9) IIEF-5 score, median (IQR) 21 (17-22) 21 (17-22) 21 (16-22) 0.09 PDE5 : phosphodiesterase 5; BMI: body mass index; s.d.: standard deviation; lIIEF-5: International Index of Erectile Function-5; IQR: interquartile range; GG: PDE5 GG polymorphism; GT: PDE5 GT polymorphism; TT: PDE5 TT polymorphism Table 5: The relationship between education level, infertility time, phosphodiesterase 5 polymorphism, and erectile dysfunction by the logistic regression analyses. Clinical characteristic Crude Adjusted OR (95% CI) P OR (95% CI) P Education level Primary school 25.68 (4.58-477.3) 0.001 - - Junior high school 1.88 (1.31-2.44) <0.001 - - High school 1.79 (1.21-2.39) <0.001 - - University Reference - - - Infertility time 3 years 1.13 (0.75-1.69) 0.14 - - PDE5 gene polymorphism GG Reference - Reference - TG 1.15 (0.86-1.53) 0.07 1.10 (0.82-1.48) 0.15 TT 1.16 (0.82-1.64) 0.12 1.13 (0.79-1.60) 0.18 The logistic regression analysis was conducted after adjusting for age, BMI, smoking, drinking, education level, and infertility time. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated. The PDE5 gene polymorphism was classified into three groups: GG (denoting PDE5 GG polymorphism), GT (representing PDE5 GT polymorphism), and TT (indicating PDE5 TT polymorphism). A "-" symbol indicates the absence of a specific group. Table 6: Distribution of phosphodiesterase 5 polymorphisms according to International Index of Erectile Function‑5 Score Frequencies IIEF-5 score range Total (n=627) GG (n=186) TG (n=301) TT (n=140) 1-11, n (%) 33 (5.3) 7 (3.8) 16 (5.3) 10 (7.1) 12-16, n (%) 84 (13.4) 24 (12.9) 39 (13.1) 21 (15.0) 17-21, n (%) 261 (41.6) 74 (39.8) 130 (43.3) 57 (40.7) 22-25, n (%) 249 (39.7) 81 (43.5) 116 (38.5) 52 (37.2) PDE5 : phosphodiesterase 5; lIIEF-5: International Index of Erectile Function-5; P values were derived from Pearson's Chi-square test. P (GG vs GT) = 0.09; P (GG VS TT) = 0.01; P (GT VS TT) = 0.26. GG: PDE5 GG polymorphism; GT: PDE5 GT polymorphism; TT: PDE5 TT polymorphism Table 7: The association between phosphodiesterase 5 TT polymorphism and severe erectile dysfunction by logistic regression analysis Clinical characteristic Crude Adjusted OR (95% CI) P OR (95% CI) P PED5 polymorphism vs IIEF-5 score GT vs Severe 1.85(0.78-3.75) 0.21 1.76(0.72-3.69) 0.2 GT vs Moderate 1.24(0.87-1.87) 0.98 1.20(0.83-1.84) 0.97 GT vs Mild 1.32(0.96-1.97) 0.67 1.31(0.95-1.95) 0.67 TT vs Severe 2.44(1.10-5.45) 0.01 2.35(1.04-5.39) 0.01 TT vs Moderate 1.35(0.97-2.04) 0.78 1.30(0.92-1.99) 0.77 TT vs Mild 1.25(0.73-1.85) 0.13 1.22(0.70-1.82) 0.13 logistic regression analysis with adjustment for age, smoking, drinking, BMI, education level, and infertility time. ED: erectile dysfunction; PDE5 : phosphodiesterase 5; GG: PDE5 GG polymorphism; GT: PDE5 GT polymorphism; TT: PDE5 TT polymorphism; OR: odds ratio; CI: confidence interval. DISCUSSION ED was a widespread obsession that affected many adult individuals worldwide. New-onset ED affected approximately 15% of individuals in the reproductive age, and it was frequently linked to an elevated risk of vasculogenic diseases ( 13 ). Studies had recently demonstrated that alterations in PDE5 G > T polymorphism were influential factors that impacted the effectiveness of PDE5 inhibitors, represented by sildenafil, following treatment for ED ( 14 ). The objective of our study was to examine the correlation between the severity of ED and PDE5 gene polymorphisms at the rs3806808 locus in a sizeable sample of men undergoing fertility assessment in andrology department. Our results validated a significant association between severe ED and the PDE5 TT polymorphism, while no substantial correlation was found between ED and the PDE5 GG or GT polymorphism. Studies on population health had revealed that the occurrence of ED exceeded 50% among males aged 40 to 70 years ( 15 ), and ranged from 14–73% in men under 40 years old ( 16 ). According to a meta-analysis study, the overall prevalence of ED in men was approximately 50%, showing an occurrence rate ranging from 20–40% prior to the age of 50 specifically in China ( 17 ). While age was a significant factor in ED prevalence, differences in study populations might contribute to variations in percentages. For instance, a study on non-diabetic young males with obesity in a cohort study conducted in a primary care setting showed that the reported prevalence was 42% ( 18 ). Other studies focusing on males diagnosed with infertility using the IIEF-5 questionnaires found prevalences ranging from 50.9–61.7% ( 19 , 20 ). Our study comprised predominantly individuals below the age of 40, with more than half of the participants recruited from male partners of couples encountering infertility for at least a year. Consistent with previous investigations employing similar eligibility criteria, the prevalence of ED in our study population was 58.9% ( 21 , 22 ). The higher prevalence observed in this study potentially indicated an elevated susceptibility to sexual dysfunction among men undergoing fertility assessment ( 23 ). Existing research had shown that genetic factors could play a role in shaping individual variations in human sexual behavior ( 24 ). The investigation of the correlation between genetic polymorphisms and sexual function had been extensively explored through the candidate gene approach. Numerous candidate genetic polymorphisms had been documented as having potential associations with the risk of developing ED ( 25 ). The G894T polymorphism of endothelial nitric oxide synthase (eNOS), an enzyme critical for vascular function, had been associated with an elevated susceptibility to ED ( 26 ). Moreover, the DD polymorphism of the angiotensin-converting enzyme (ACE), which was involved in the renin-angiotensin system, had been observed at a higher frequency among men diagnosed with vascular ED ( 27 ). Nevertheless, a meta-analysis that included 1039 individuals with ED and 927 healthy controls concluded that there was no significant association between the D polymorphism in the ACE gene and an elevated risk of ED ( 28 ). In patients with vascular ED, the prevalence of the PDE5 677TT polymorphism was higher in comparison to those without vascular ED (15.8% vs. 11.4%) ( 29 ). The G to T substitution at rs3806808 locus in PDE5 gene resulted in impaired function of both vascular smooth muscle cells and endothelial cells. The increase in plasma cGMP levels resulting from this mutation contributed to intima-media thickening, leading to reduced blood flow within the erectile tissue of the corpora cavernosa ( 30 ). One study investigated another PDE5 gene polymorphism (rs12646525) in association with vasculogenic ED ( 30 ). Their findings revealed that the frequencies of TT, CT, and CC did not significantly differ between the ED and non-ED groups. However, individuals with the CT and CC polymorphisms had a significantly increased risk of severe ED. It was important to note that the sample size (125 cases and 236 controls) was not large enough to draw robust epidemiological conclusions. However, despite reports linking the PDE5 GG polymorphism to increased cGMP levels, no significant association was found between the PDE5 G polymorphism and the risk of ED. In our study, we observed a positive correlation between the PDE5 TT polymorphism and an increased risk of severe ED, aligning with previous research and benefiting from a relatively large sample size ( 31 ). Moreover, the elevated plasma cGMP concentration caused by the PDE5 TT polymorphism might contribute to the heightened risk of severe ED, considering the role of PDE5 in cGMP metabolism. On the other hand, an additional study with a relatively small sample size of middle-aged to elderly men (mean ± SD: 51.2 ± 6.5 years) observed an association between the PDE5 T polymorphism and the risk of ED but did not find a correlation with plasma luteinizing hormone (LH) levels ( 30 ). We attributed these inconsistent observations to disparities in the study populations and sample sizes. Associations had been identified between genetic factors and the risk of ED, with these gene polymorphisms potentially influencing the response to PED5 inhibitors, which are commonly employed for the treatment of ED. In a recent systematic review encompassing 12 studies and involving 1535 men with ED, it was determined that gene polymorphisms, including the PDE5 gene polymorphism, significantly impacted the response to PDE5 inhibitor treatment. In their observations, Lombardo et al noted that young patients with the PDE5 TT polymorphism, unresponsive to PDE5 inhibitors ( 32 ), experienced improved symptoms of ED through the administration of vitamin B6 and folic acid. However, more comprehensive studies were required to explore these findings in greater depth. The identification of PDE5 gene polymorphisms might hold potential for the diagnosis of ED in younger patients. Several strengths were apparent in this study. To start, the mean age of the participants involved in our study was 29.8 years, which reduced the potential confounding effect of age on the risk of ED. Then, we implemented strict exclusion criteria that excluded participants with hypertension, diabetes, and hyperlipidemia. This enabled the focus on the independent role of the PDE5 gene polymorphism in the risk of ED. Lastly, the large population-based design utilized in our study ensured a robust exploration of the association between the PDE5 T polymorphism and the severity of ED. By accounting for potential confounding factors such as age, lifestyle factors (smoking and drinking), BMI, educational level, and infertility time, we enhanced the statistical power of our findings. Several limitations existed in this study. As a cross-sectional study, it did not establish a cause-and-effect relationship between variables. Furthermore, the study sample comprised men undergoing infertility assessments at a singular andrology department in north China, potentially restricting the generalizability of the findings to other regions or populations. For a comprehensive understanding, additional studies involving diverse populations were required. Thirdly, the study did not assess the effects of treatment with PDE5 inhibitors, despite the observed association between the PDE5 gene polymorphism and the risk of ED. Furthermore, this study did not assess important metabolic and hormonal parameters, such as total testosterone levels and thyroid function. Additionally, penile ultrasound examination results were not taken into account. Finally, there might have been a potential for recall bias when gathering data on the severity of ED using the IIEF-5 questionnaire. Addressing these limitations in future research will enable a more comprehensive assessment of the topic. CONCLUSIONS The findings of this study suggest a positive association between the PDE5 TT polymorphism and an increased risk of severe ED. The identification of PDE5 gene polymorphisms could serve as valuable additional information for the clinical diagnosis of ED in routine practice. Declarations COMPETING INTERESTS All authors declare no competing interests. Ethics Approval and Consent to Participate: This study was approved by the Ethics Committee of the First Affiliated Hospital of Shandong Second Medical University of China (Approval No. 20220521-JY-001). Written informed consent was obtained from all participants prior to their inclusion in the study. Consent to Publish Informed consent was obtained from all individual participants included in the study. Funding Declaration This work was supported by the grants from the Key Common Technology Research and Development Project in Hefei City, China (GJ2022SM09) and 2023 Anhui Province Clinical Key Specialty Fund. Author Contribution The research study was designed by XF, MH, and FG. Data acquisition was contributed by XF, MH, and HZ. Data analysis was conducted by XF, MH, and FG were responsible for writing the paper. XF, MH, and FG revised the manuscript and provided comments. All authors have read and approved the final manuscript. Acknowledgement This work was supported by the grants from the Key Common Technology Research and Development Project in Hefei City, China (GJ2022SM09) and 2023 Anhui Province Clinical Key Specialty Fund Data Availability The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. References McCabe MP, Sharlip ID, Atalla E, Balon R, Fisher AD, Laumann E, et al. Definitions of Sexual Dysfunctions in Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. J. Sex. Med. 2016; 13: 135-43. Lotti F, Maggi M. Sexual dysfunction and male infertility. Nat. Rev. Urol. 2018; 15: 287-307. Bodie JA, Beeman WW, Monga M. Psychogenic erectile dysfunction. Int. J. Psychiatr. Med. 2003; 33: 273-93. Terentes-Printzios D, Ioakeimidis N, Rokkas K, Vlachopoulos C. Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs. Nat. Rev. Cardiol. 2022; 19: 59-74. Gur S, Alzweri L, Yilmaz-Oral D, Kaya-Sezginer E, Abdel-Mageed A, Dick B, et al. Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum. Andrology 2020; 8: 1824-33. Liu R, Kang YL, Chen L. Activation mechanism of human soluble guanylate cyclase by stimulators and activators. Nat. Commun. 2021; 12: 10. Lombardo R, Tema G, De Nunzio C. Phosphodiesterases 5 Inhibitors and Erectile Dysfunction Recovery after Pelvic Surgery: Future Perspectives for New Drugs and New Formulations. Curr. Drug Targets 2021; 22: 31-7. Bajraktari G, Burhenne J, Bugert P, Haefeli WE, Weiss J. Cyclic guanosine monophosphate modulates accumulation of phosphodiesterase 5 inhibitors in human platelets. Biochemical Pharmacology 2017; 145: 54-63. Van de Voorde J, Boydens C, Pauwels B, Vanden Daele L. Inhibition of Cyclic GMP Export by Multidrug Resistance Protein 4: a New Strategy to Treat Erectile Dysfunction? J. Vasc. Res. 2017; 54: 69-. Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile Dysfunction: AUA Guideline. The Journal of urology 2018; 200: 633-41. Chen Y, Li J, Li TY, Long JX, Liao JL, Wei GH, et al. Association between homocysteine, vitamin B12, folic acid and erectile dysfunction: a cross-sectional study in China. BMJ Open 2019; 9: 8. Salvi F, Sarzani R, Giorgi R, Donatelli G, Pietrucci F, Micheli A, et al. Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5). International journal of impotence research 2004; 16: 412-7. Kessler A, Sollie S, Challacombe B, Briggs K, Van Hemelrijck M. The global prevalence of erectile dysfunction: a review. BJU international 2019; 124: 587-99. Ahmed WS, Geethakumari AM, Biswas KH. Phosphodiesterase 5 (PDE5): Structure-function regulation and therapeutic applications of inhibitors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2021; 134: 111128. Goldstein I, Goren A, Li VW, Tang WY, Hassan TA. Epidemiology Update of Erectile Dysfunction in Eight Countries with High Burden. Sexual Medicine Reviews 2020; 8: 48-58. Colson MH, Cuzin B, Faix A, Grellet L, Huyghes E. Current epidemiology of erectile dysfunction, an update. Sexologies 2018; 27: e7-e13. Wang W, Fan J, Huang G, Zhu X, Tian Y, Tan H, et al. Meta-Analysis of Prevalence of Erectile Dysfunction in Mainland China: Evidence Based on Epidemiological Surveys. Sexual medicine 2017; 5: e19-e30. Alhomaid AM, Moin Ahmed M. Prevalence of Non-diabetic Hyperglycemia in Young Adults and Its Impact on Periodontal Health. Cureus 2024; 16: e53847. Kaltsas A, Zachariou A, Dimitriadis F, Chrisofos M, Sofikitis N. Empirical Treatments for Male Infertility: A Focus on Lifestyle Modifications and Medicines. Diseases (Basel, Switzerland) 2024; 12. Focusing on male infertility. Nat. Rev. Urol. 2024; 21: 61-. Liu R, Rizzo S, Whipple S, Pal N, Pineda AL, Lu M, et al. Evaluating eligibility criteria of oncology trials using real-world data and AI. Nature 2021; 592: 629-33. Hu K, Zhao L, Zhou Q, Mei F, Gao Q, Chen F, et al. Inconsistencies in study eligibility criteria are common between non-Cochrane systematic reviews and their protocols registered in PROSPERO. Research synthesis methods 2021; 12: 394-405. Li JZ, Maguire TA, Zou KH, Lee LJ, Donde SS, Taylor DG. Prevalence, Comorbidities, and Risk Factors of Erectile Dysfunction: Results from a Prospective Real-World Study in the United Kingdom. International journal of clinical practice 2022; 2022: 5229702. Foulkes L, Blakemore S-J. Studying individual differences in human adolescent brain development. Nature Neuroscience 2018; 21: 315-23. Tabor HK, Risch NJ, Myers RM. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nature Reviews Genetics 2002; 3: 391-7. Ma Q, lv J, Huang K, Guo H, Yang W, Luo W, et al. Endothelial nitric oxide synthase gene G894T polymorphism and risk assessment for pregnancy-induced hypertension: evidence from 11 700 subjects. Hypertension Research 2016; 39: 899-906. Kumari N, Yadav A, Ahirwar R, Sagar SK, Mondal PR. Angiotensin converting enzyme (ACE) insertion / deletion (I/D) polymorphism and its association with cardiovascular adversities – A systematic review. Human Gene 2022; 34: 201117. Lin CJ, Chang YC, Cheng TY, Lo K, Liu SJ, Yeh TL. The association between metabolically healthy obesity and risk of cancer: A systematic review and meta-analysis of prospective cohort studies. Obesity reviews : an official journal of the International Association for the Study of Obesity 2020; 21: e13049. Nehra A. Erectile Dysfunction and Cardiovascular Disease: Efficacy and Safety of Phosphodiesterase Type 5 Inhibitors in Men With Both Conditions. Mayo Clinic Proceedings 2009; 84: 139-48. Mostafa T, Hassan A, Alghobary MF, Abdelrahman SH. Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal. Sexual Medicine Reviews 2020; 8: 573-85. Zhang Z, Huang W, Huang D, Xu Z, Xie Q, Tan X, et al. Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription. Communications Biology 2025; 8: 85. Kolontarev K, Govorov A, Kasyan G, Priymak D, Pushkar D. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors. Central European journal of urology 2016; 69: 398-403. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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-6780139","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481346888,"identity":"4e41a4a1-a2a8-4755-ba80-7ee0a30c79da","order_by":0,"name":"Xianchun Fu","email":"","orcid":"","institution":"WeiFang People's Hospital, Shandong Second Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xianchun","middleName":"","lastName":"Fu","suffix":""},{"id":481346889,"identity":"9cbff75a-d005-40c5-9bf1-cfa93a2e698a","order_by":1,"name":"Mingyun Hong","email":"","orcid":"","institution":"Hefei Maternal and Child Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mingyun","middleName":"","lastName":"Hong","suffix":""},{"id":481346891,"identity":"2a43432a-bf33-4ce2-9c8b-f249eb707ab0","order_by":2,"name":"Han Zhang","email":"","orcid":"","institution":"The Affiliated Hospital of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Zhang","suffix":""},{"id":481346892,"identity":"11790dc6-3d68-4291-afe3-deab93a004e6","order_by":3,"name":"Feng Gao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYBAC9gYYi5nxAZC04eHnb8ClGAJ4DsC1MBsAyTQZyRkHcKpG08IA1nLYxqAhgYAW9t7DL7/U2CT2szMzfi74dZ7HgOEA44ePOXi08JxLs5Y5lpY4s5mZWXpm320ec+YGZsmZ23BrsZfIMTOWYDucu+Ew/wFp3p7bPJYNB9iYefFo4ZF/A9Ty73Du/sPMzL95e87xGBxIIKBFgsf44cc2oC3MzGzSPD8OEKGFJ8eMmbEvrX7GYWY2a96GZB7JGQeb8fqFh/2M8ccf32yM+fsPM9/m+WNnz8/ffPDDRzxagADoHhiTsQ1MNuBVDwTMH3/A2X8IKR4Fo2AUjIKRCAAKUk/jFXKQsQAAAABJRU5ErkJggg==","orcid":"","institution":"WeiFang People's Hospital, Shandong Second Medical University","correspondingAuthor":true,"prefix":"","firstName":"Feng","middleName":"","lastName":"Gao","suffix":""}],"badges":[],"createdAt":"2025-05-30 02:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6780139/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6780139/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100238748,"identity":"fe7df617-df2b-4c9b-9c92-a0b495ae771f","added_by":"auto","created_at":"2026-01-14 12:55:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1018944,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6780139/v1/384f63d7-6639-4aec-9750-8c708c7ebfb8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Study on correlation between gene polymorphism of PDE5 rs3806808 locus and erectile dysfunction","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe condition of erectile dysfunction (ED) was defined by the difficulty in attaining or sustaining an erection suitable for fulfilling sexual activity (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Among adult males, ED was a prevalent issue, affecting approximately 12\u0026ndash;19% of individuals within the reproductive age group (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Various underlying mechanisms contribute to ED, including vascular, neurogenic, and psychogenic factors, with vascular causes being the most prevalent(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Factors related to lifestyle and conditions like diabetes, hypertension, and dyslipidemia were significant factors contributing to vascular ED (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe reduced function of the nitric oxide (NO)-dependent relaxation system was a primary cause of ED (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Upon sexual stimulation, the activation of the constitutive nitric oxide synthase (NOS3) enzyme in the endothelial cells was sustained due to the blood vessels and sinusoidal pressures exerted on them. NO triggered the activation of soluble guanylate cyclase (sGC) and promotes the production of cyclic guanosine monophosphate (cGMP) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Phosphodiesterase 5 (\u003cem\u003ePDE5\u003c/em\u003e) was responsible for the breakdown and elimination of cGMP. Research had demonstrated the significant involvement of \u003cem\u003ePDE5\u003c/em\u003e in the progression of ED. \u003cem\u003ePDE5\u003c/em\u003e inhibitors could reduce the hydrolysis of cGMP and prolong the relaxation time of penile blood vessels and corpus cavernosum smooth muscle, effectively maintaining penile erection(\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003ePDE5\u003c/em\u003e inhibitors, represented by sildenafil, had shown great efficacy in treating ED, but there were also some patients with poor response, which might be due to the polymorphism of the \u003cem\u003ePDE5\u003c/em\u003e coding gene. Researches had shown that polymorphism of the \u003cem\u003ePDE5\u003c/em\u003e at rs3806808 locus was an important factor affecting the efficacy of sildenafil(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, there were currently few studies on the relationship between \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism with rs3806808 mutation and ED. This study analyzes the relationship between \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism at rs3806808 locus and the onset of ED.\u003c/p\u003e"},{"header":"PARTICIPANTS AND METHODS","content":"\u003cp\u003e\u003cem\u003eParticipants\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e627 individuals from the andrology department undergoing fertility assessment at The First Affiliated Hospital of Shandong Second Medical University in China (Shandong, China) between May 2023 and March 2024 were enrolled in this cross-sectional investigation. Included in this study were participants who completed the survey. Exclusion criteria consisted of: (1) males aged 50 years or older; (2) males with hypertension, high cholesterol, or diabetes; or (3) males with a prior history of urinary or genital infections and varicocele. An andrologist conducted physical examinations on all participants. Approval for the research was obtained from the Ethics Committee at the First Affiliated Hospital of Shandong Second Medical University of China (Approval No. 20220521-JY-001). The study was conducted in accordance with the Declaration of Helsinki and its later amendments. All individuals were asked to provide written informed consent before participating in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuestionnaires administration and ED evaluation\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA comprehensive questionnaire covering various aspects was completed by the participants in this study. These included demographic characteristics such as age, weight, height, educational level, and infertility time. Factors related to lifestyle such as smoking and drinking habits were also assessed. Furthermore, participants provided information on their medical history, including conditions like hypertension, diabetes, hyperlipidemia, varicoceles, cryptorchidism, and testicular cancer. To assess erectile function, the Chinese version of the International Index of Erectile Function-5 (IIEF-5) questionnaire was utilized. The focus of the IIEF-5 questionnaire includes parameters such as confidence in attaining and sustaining an erection, rigidity of erections, ability to maintain an erection during sexual intercourse, frequency of maintaining erections, and satisfaction with sexual intercourse. The total score on the questionnaire ranged from 1 to 25. Each participant completed the IIEF-5 questionnaire independently to minimize any potential influence came from the doctors. ED was classified based on the IIEF-5 score as follows: no symptoms (score 22-25), mild symptoms (score 17-21), moderate symptoms (score 12-16), and severe symptoms (score 1-11).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMeasurements of the PDE5 G\u0026gt;T variant at rs3806808 locus\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt the commencement of the study, all participants were asked to undergo a blood sample collection by venipuncture. The collected samples were utilized for the extraction of total genomic DNA utilizing the QIAamp DNA Mini Kit (Qiagen, Hilden, Germany). Detection of the \u003cem\u003ePDE5\u003c/em\u003e rs3806808 G\u0026gt;T variant was carried out using fluorescence polymerase chain reaction (PCR) following the protocol provided by the manufacturer (Talde Medical Group, Shenzhen, China).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analyses\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe body mass index (BMI) was calculated by dividing the weight in kilograms by the square of the height in meters. The participants were categorized into two groups based on their IIEF-5 scores: the ED group and the non-ED group. Frequencies were used to represent qualitative variables, whereas mean \u0026plusmn; standard deviation (s.d.) was employed to report quantitative variables. Student\u0026apos;s t-test was used to compare parametric continuous data, while Pearson\u0026apos;s chi-squared test was employed to analyze categorical data. To evaluate the relationship between ED and the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism, logistic regression analysis was conducted. Two models were employed: a crude model and an adjusted model. The adjusted model incorporated covariates such as age, BMI, smoking, drinking, education level, and infertility time. Statistical analyses were carried out using GraphPad Prism 9.0 software (GraphPad Software, San Diego, CA, USA). The significance level was set at a \u003cem\u003eP\u003c/em\u003e-value of less than 0.05.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 627 male participants (mean [s.d.] age: 29.8 [3.3] years) were enrolled in this research (\u003cstrong\u003eTable 1\u003c/strong\u003e). The participants were divided into two groups based on their IIEF-5 score: the non-ED group (\u003cem\u003en\u003c/em\u003e = 258) and the ED group (\u003cem\u003en\u003c/em\u003e = 369). The age comparison between the non-ED group (mean [s.d.] age: 29.9 [3.2] years; \u003cem\u003eP\u003c/em\u003e = 0.71) and the ED group (mean [s.d.] age: 29.8 [3.4] years) did not reveal any significant differences. Furthermore, the non-ED group exhibited a slightly higher BMI, although this disparity was not deemed statistically significant. The two groups showed comparable Factors related to lifestyle, such as tobacco use and alcohol consumption. Notably, the non-ED group exhibited a notably higher education level (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001), which aligns with the results of a previous study (11). Moreover, there were no significant disparities noted in the genotypic frequencies of the \u003cem\u003ePDE5\u003c/em\u003e rs3806808 polymorphism (TT, GT, and GG) between non-ED groups and the ED group (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.26).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudies had reported variations in enzyme activity levels amongst the different \u003cem\u003ePDE5\u003c/em\u003e rs3806808 polymorphisms, Moreover, our findings further corroborated individuals with the \u003cem\u003ePDE5\u003c/em\u003e TT gene type had higher levels of serum cGMP than men with the \u003cem\u003ePDE5\u003c/em\u003e GT and GG gene types (\u003cstrong\u003eTable 2\u003c/strong\u003e). Despite having a relatively high number of cases, our participants exhibited a lower prevalence of the \u003cem\u003ePDE5\u003c/em\u003e T allele compared to the prior study(12) (\u003cstrong\u003eTable 3\u003c/strong\u003e). \u003cstrong\u003eTable 4\u003c/strong\u003e displayed a summary of the demographic characteristics of participants, categorized according to their \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms, is presented. The results of a binary logistic regression analysis, investigating the correlation between ED and variables such as education level, infertility time, and the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism, were presented in \u003cstrong\u003eTable 5\u003c/strong\u003e. Compared to the reference group (university), men with a lower education level (primary school, junior high school, and high school) exhibited an increased risk of ED (odds ratio [OR] = 25.68;\u003cem\u003e\u0026nbsp;P\u0026nbsp;\u003c/em\u003e= 0.001, OR = 1.88,\u003cem\u003e\u0026nbsp;P\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001; OR = 1.79,\u003cem\u003e\u0026nbsp;P\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001, respectively). Conversely, no significant correlation was found between ED and infertility time (\u003cem\u003eP\u003c/em\u003e = 0.15). Both crude and adjusted models indicated that the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism was not significantly linked to the risk of ED (crude, GG \u003cem\u003evs\u003c/em\u003e GT [\u003cem\u003eP\u003c/em\u003e = 0.07], GG \u003cem\u003evs\u0026nbsp;\u003c/em\u003eTT [\u003cem\u003eP\u003c/em\u003e = 0.12]; adjusted, GG \u003cem\u003evs\u003c/em\u003e GT [\u003cem\u003eP\u003c/em\u003e = 0.15], GG \u003cem\u003evs\u003c/em\u003e TT [\u003cem\u003eP\u003c/em\u003e = 0.18]). Further explorations were carried out to examine the association between the distribution of \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms and the severity of ED, as determined by the categorizations of the IIEF-5 scores (1-11: severe, 12-16: moderate, 17-21: mild). In individuals with severe and moderate ED, there was a notably higher frequency of homozygous TT polymorphism (\u003cem\u003eP\u003c/em\u003e = 0.01; \u003cstrong\u003eTable 6\u003c/strong\u003e). However, there was no significant difference in the severity of ED between men with \u003cem\u003ePDE5\u003c/em\u003e GT (\u003cem\u003eP\u003c/em\u003e = 0.09) and TT polymorphisms (\u003cem\u003eP\u003c/em\u003e = 0.26). After adjusting for potential confounding variables, logistic regression analysis demonstrated a significant positive association between the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism and severe ED (crude OR = 2.44, 95% CI: 1.10-5.45, \u003cem\u003eP\u003c/em\u003e = 0.01; adjusted OR = 2.35, 95% CI: 1.04-5.39, \u003cem\u003eP\u003c/em\u003e = 0.01; \u003cstrong\u003eTable 7\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Demographic characteristics of the study population\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"530\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u003cem\u003eDemographic characteristic\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e\u003cem\u003eTotal individuals (n=627)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e\u003cem\u003eED group (n=369)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e\u003cem\u003eNon-ED group (n=258)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eAge(year), mean\u0026plusmn;s.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e29.8\u0026plusmn;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e29.8\u0026plusmn;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e29.9\u0026plusmn;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eAge (year), \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u0026lt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e250 (39.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e142 (38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e108 (41.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e30-39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e344 (54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e205 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e139 (53.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u0026ge;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e33 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e22 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e11 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eBMI (kg\u0026middot;m\u003csup\u003e-2\u003c/sup\u003e), mean\u0026plusmn;s.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e23.5\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e23.3\u0026plusmn;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e23.7\u0026plusmn;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eAlcohol amount, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eNondrinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e290 (46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e172 (46.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e117 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eDrinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e337 (53.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e197 (53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e140 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eSmoking amount, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eNonsmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e347 (55.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e200 (54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e147 (57.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e280 (44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e169 (45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e111 (42.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eEducation level, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003ePrimary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e15 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e14 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e1 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e137 (21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e95 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e42 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e108 (17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e72 (19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e36 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eUniversity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e367 (58.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e188 (51.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e179 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eInfertility time, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u0026lt;l year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e303 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e172 (46.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e131 (50.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e163 (26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e95 (25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e68 (26.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e2-3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e86 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e55 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e30 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u0026gt;3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e75 (12.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e47 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e29 (11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003e\u003cem\u003ePDE5\u003c/em\u003e gene\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;polymorphism, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e186 (29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e102 (27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e84 (32.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e301 (48.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e182 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e119 (46.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e140 (22.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e85 (23.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e55 (21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37.4291%;\"\u003e\n \u003cp\u003eIIEF-5 score, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.3365%;\"\u003e\n \u003cp\u003e20 (17-24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e17 (15-21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.3119%;\"\u003e\n \u003cp\u003e24 (22-25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.6106%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e values were assessed using Pearson\u0026apos;s Chi-square test and Student\u0026apos;s \u003cem\u003et\u003c/em\u003e-test. s.d.: standard deviation; IQR: interquartile range; ED: erectile dysfunction; BMI: body mass index; IIEF-5: International Index of Erectile Function-5; \u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; GG signifies the \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism, GT represents the \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism, and TT denotes the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e \u003cstrong\u003eCyclic guanosine monophosphate levels\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in participants based on the phosphodiesterase 5 rs3806808 polymorphism\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.3971%;\"\u003e\n \u003cp\u003e\u003cem\u003eVariable\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46.9314%;\"\u003e\n \u003cp\u003e\u003cem\u003ePDE5 rs3806808 polymorphism\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.8159%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.3971%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 13.7184%;\"\u003e\n \u003cp\u003e\u003cem\u003eGG (n=4)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.148%;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;GT (n=8)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.065%;\"\u003e\n \u003cp\u003e\u003cem\u003eTT (n=6)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.8159%;\"\u003e\n \u003cp\u003e\u003cem\u003e \u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 20.3971%;\"\u003e\n \u003cp\u003ecGMP\u0026nbsp;(\u0026mu;mol\u003csup\u003e-1\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.7184%;\"\u003e\n \u003cp\u003e19.5\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.148%;\"\u003e\n \u003cp\u003e19.0\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.065%;\"\u003e\n \u003cp\u003e25.6\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.9278%;\"\u003e\n \u003cp\u003e0.0006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.8159%;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e, GG VS GT; \u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e, GG VS TT; \u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e, GT VS TT. \u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; cGMP: cyclic guanosine monophosphate; GG: \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism; GT: \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism; TT: \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Comparing the distribution of phosphodiesterase 5 polymorphism between our study population and a previous study of general men\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"550\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003e\u003cem\u003ePDE5 gene polymorphisms\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e\u003cem\u003eOur study,\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e\u003cem\u003ePrior study,\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e186(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e12 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003eGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e301(48.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e39 (47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e140(22.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e32 (38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003eAllele G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e673(53.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e32 (37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 27.6867%;\"\u003e\n \u003cp\u003eAllele T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.6903%;\"\u003e\n \u003cp\u003e581(46.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.4117%;\"\u003e\n \u003cp\u003e51 (62.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2113%;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; GT: \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism; TT: \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism; GG: \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Demographic Profile of Participants Based on Phosphodiesterase 5 Polymorphism.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"559\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003e\u003cem\u003eClinical characteristic\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e\u003cem\u003eGG (n=186)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e\u003cem\u003eGT (n=301)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e\u003cem\u003eTT (n=140)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eAge (year), mean\u0026plusmn;s.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e29.9\u0026plusmn;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e29.8\u0026plusmn;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e30.0\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eBMI (kg\u0026middot;m\u003csup\u003e-2\u003c/sup\u003e), mean\u0026plusmn;s.d.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e23.2\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e23.7\u0026plusmn;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e23.5\u0026plusmn;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eAlcohol amount, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eNondrinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e89 (47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e140 (46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e118 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eDrinking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e97 (52.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e161 (53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e79 (56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eSmoking amount,\u003cem\u003e\u0026nbsp;n\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eNonsmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e99 (53.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e173 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e76 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e87 (46.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e128 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e64 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eEducation level, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003ePrimary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e3 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e9 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e2 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e35 (18.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e70 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e33 (23.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e33 (17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e49 (16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e26 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003euniversity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e115 (58.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e173 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e79 (56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eInfertility time, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003e\u0026lt;l year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e90 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e146 (48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e67 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003e1 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e49 (26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e78 (25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e36 (25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003e2-3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e24 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e42 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e19 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003e\u0026gt;3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e23 (12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e35 (11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e18 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33.75%;\"\u003e\n \u003cp\u003eIIEF-5 score, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e21 (17-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6786%;\"\u003e\n \u003cp\u003e21 (17-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4286%;\"\u003e\n \u003cp\u003e21 (16-22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.1429%;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; BMI: body mass index; s.d.: standard deviation; lIIEF-5: International Index of Erectile Function-5; IQR: interquartile range; GG: \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism; GT: \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism; TT: \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: The relationship between education level, infertility time, phosphodiesterase 5 polymorphism, and erectile dysfunction by the logistic regression analyses.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cem\u003eClinical characteristic\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cem\u003eCrude\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 177px;\"\u003e\n \u003cp\u003e\u003cem\u003eAdjusted\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95% CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95% CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eEducation level\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003ePrimary school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e25.68 (4.58-477.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.88 (1.31-2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.79 (1.21-2.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eUniversity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003eInfertility time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026lt;l year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1-2 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e0.95 (0.70-1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2-3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.28 (0.87-1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026gt;3 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.13 (0.75-1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cem\u003ePDE5\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003egene polymorphism\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.15 (0.86-1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e1.10 (0.82-1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e1.16 (0.82-1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 60px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e1.13 (0.79-1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe logistic regression analysis was conducted after adjusting for age, BMI, smoking, drinking, education level, and infertility time. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated. The \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism was classified into three groups: GG (denoting \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism), GT (representing \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism), and TT (indicating \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism). A \u0026quot;-\u0026quot; symbol indicates the absence of a specific group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6: Distribution of phosphodiesterase 5 polymorphisms according to International Index of Erectile Function‑5 Score Frequencies\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003eIIEF-5 score range\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003eTotal (n=627)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cem\u003eGG (n=186)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eTG (n=301)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cem\u003eTT (n=140)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e1-11, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e33 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e7 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e16 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e10 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e12-16, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e84 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e24 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e39 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e21 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e17-21, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e261 (41.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e74 (39.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e130 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e57 (40.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e22-25, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e249 (39.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e81 (43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e116 (38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e52 (37.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; lIIEF-5: International Index of Erectile Function-5; \u003cem\u003eP\u003c/em\u003e values were derived from Pearson\u0026apos;s Chi-square test. \u003cem\u003eP\u003c/em\u003e (GG \u003cem\u003evs\u003c/em\u003e GT) = 0.09; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e(GG VS TT) = 0.01; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e(GT VS TT) = 0.26. GG: \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism; GT: \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism; TT: \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 7: The association between phosphodiesterase 5 TT polymorphism and severe erectile dysfunction by logistic regression analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"548\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cem\u003eClinical characteristic\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 195px;\"\u003e\n \u003cp\u003e\u003cem\u003eCrude\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cem\u003eAdjusted\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95% CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cem\u003eOR (95% CI)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003ePED5 polymorphism \u003cem\u003evs\u003c/em\u003e IIEF-5 score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eGT \u003cem\u003evs\u003c/em\u003e Severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.85(0.78-3.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e1.76(0.72-3.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eGT \u003cem\u003evs\u003c/em\u003e Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.24(0.87-1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e1.20(0.83-1.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eGT \u003cem\u003evs\u003c/em\u003e Mild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.32(0.96-1.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e1.31(0.95-1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eTT \u003cem\u003evs\u0026nbsp;\u003c/em\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2.44(1.10-5.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e2.35(1.04-5.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eTT \u003cem\u003evs\u003c/em\u003e Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.35(0.97-2.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e1.30(0.92-1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 168px;\"\u003e\n \u003cp\u003eTT \u003cem\u003evs\u003c/em\u003e Mild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.25(0.73-1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e1.22(0.70-1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003elogistic regression analysis with adjustment for age, smoking, drinking, BMI, education level, and infertility time. ED: erectile dysfunction; \u003cem\u003ePDE5\u003c/em\u003e: phosphodiesterase 5; GG: \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism; GT: \u003cem\u003ePDE5\u003c/em\u003e GT polymorphism; TT: \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism; OR: odds ratio; CI: confidence interval.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eED was a widespread obsession that affected many adult individuals worldwide. New-onset ED affected approximately 15% of individuals in the reproductive age, and it was frequently linked to an elevated risk of vasculogenic diseases (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Studies had recently demonstrated that alterations in \u003cem\u003ePDE5\u003c/em\u003e G\u0026thinsp;\u0026gt;\u0026thinsp;T polymorphism were influential factors that impacted the effectiveness of \u003cem\u003ePDE5\u003c/em\u003e inhibitors, represented by sildenafil, following treatment for ED (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The objective of our study was to examine the correlation between the severity of ED and \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms at the rs3806808 locus in a sizeable sample of men undergoing fertility assessment in andrology department. Our results validated a significant association between severe ED and the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism, while no substantial correlation was found between ED and the \u003cem\u003ePDE5\u003c/em\u003e GG or GT polymorphism.\u003c/p\u003e \u003cp\u003eStudies on population health had revealed that the occurrence of ED exceeded 50% among males aged 40 to 70 years (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), and ranged from 14\u0026ndash;73% in men under 40 years old (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). According to a meta-analysis study, the overall prevalence of ED in men was approximately 50%, showing an occurrence rate ranging from 20\u0026ndash;40% prior to the age of 50 specifically in China (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While age was a significant factor in ED prevalence, differences in study populations might contribute to variations in percentages. For instance, a study on non-diabetic young males with obesity in a cohort study conducted in a primary care setting showed that the reported prevalence was 42% (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Other studies focusing on males diagnosed with infertility using the IIEF-5 questionnaires found prevalences ranging from 50.9\u0026ndash;61.7% (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Our study comprised predominantly individuals below the age of 40, with more than half of the participants recruited from male partners of couples encountering infertility for at least a year. Consistent with previous investigations employing similar eligibility criteria, the prevalence of ED in our study population was 58.9% (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The higher prevalence observed in this study potentially indicated an elevated susceptibility to sexual dysfunction among men undergoing fertility assessment (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eExisting research had shown that genetic factors could play a role in shaping individual variations in human sexual behavior (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The investigation of the correlation between genetic polymorphisms and sexual function had been extensively explored through the candidate gene approach. Numerous candidate genetic polymorphisms had been documented as having potential associations with the risk of developing ED (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). The G894T polymorphism of endothelial nitric oxide synthase (eNOS), an enzyme critical for vascular function, had been associated with an elevated susceptibility to ED (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Moreover, the DD polymorphism of the angiotensin-converting enzyme (ACE), which was involved in the renin-angiotensin system, had been observed at a higher frequency among men diagnosed with vascular ED (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Nevertheless, a meta-analysis that included 1039 individuals with ED and 927 healthy controls concluded that there was no significant association between the D polymorphism in the ACE gene and an elevated risk of ED (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). In patients with vascular ED, the prevalence of the \u003cem\u003ePDE5\u003c/em\u003e 677TT polymorphism was higher in comparison to those without vascular ED (15.8% vs. 11.4%) (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe G to T substitution at rs3806808 locus in \u003cem\u003ePDE5\u003c/em\u003e gene resulted in impaired function of both vascular smooth muscle cells and endothelial cells. The increase in plasma cGMP levels resulting from this mutation contributed to intima-media thickening, leading to reduced blood flow within the erectile tissue of the corpora cavernosa (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). One study investigated another \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism (rs12646525) in association with vasculogenic ED (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Their findings revealed that the frequencies of TT, CT, and CC did not significantly differ between the ED and non-ED groups. However, individuals with the CT and CC polymorphisms had a significantly increased risk of severe ED. It was important to note that the sample size (125 cases and 236 controls) was not large enough to draw robust epidemiological conclusions. However, despite reports linking the \u003cem\u003ePDE5\u003c/em\u003e GG polymorphism to increased cGMP levels, no significant association was found between the \u003cem\u003ePDE5\u003c/em\u003e G polymorphism and the risk of ED. In our study, we observed a positive correlation between the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism and an increased risk of severe ED, aligning with previous research and benefiting from a relatively large sample size (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Moreover, the elevated plasma cGMP concentration caused by the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism might contribute to the heightened risk of severe ED, considering the role of \u003cem\u003ePDE5\u003c/em\u003e in cGMP metabolism. On the other hand, an additional study with a relatively small sample size of middle-aged to elderly men (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD: 51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5 years) observed an association between the \u003cem\u003ePDE5\u003c/em\u003e T polymorphism and the risk of ED but did not find a correlation with plasma luteinizing hormone (LH) levels (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). We attributed these inconsistent observations to disparities in the study populations and sample sizes.\u003c/p\u003e \u003cp\u003eAssociations had been identified between genetic factors and the risk of ED, with these gene polymorphisms potentially influencing the response to PED5 inhibitors, which are commonly employed for the treatment of ED. In a recent systematic review encompassing 12 studies and involving 1535 men with ED, it was determined that gene polymorphisms, including the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism, significantly impacted the response to \u003cem\u003ePDE5\u003c/em\u003e inhibitor treatment. In their observations, Lombardo et al noted that young patients with the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism, unresponsive to \u003cem\u003ePDE5\u003c/em\u003e inhibitors (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), experienced improved symptoms of ED through the administration of vitamin B6 and folic acid. However, more comprehensive studies were required to explore these findings in greater depth. The identification of \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms might hold potential for the diagnosis of ED in younger patients.\u003c/p\u003e \u003cp\u003eSeveral strengths were apparent in this study. To start, the mean age of the participants involved in our study was 29.8 years, which reduced the potential confounding effect of age on the risk of ED. Then, we implemented strict exclusion criteria that excluded participants with hypertension, diabetes, and hyperlipidemia. This enabled the focus on the independent role of the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism in the risk of ED. Lastly, the large population-based design utilized in our study ensured a robust exploration of the association between the \u003cem\u003ePDE5\u003c/em\u003e T polymorphism and the severity of ED. By accounting for potential confounding factors such as age, lifestyle factors (smoking and drinking), BMI, educational level, and infertility time, we enhanced the statistical power of our findings.\u003c/p\u003e \u003cp\u003eSeveral limitations existed in this study. As a cross-sectional study, it did not establish a cause-and-effect relationship between variables. Furthermore, the study sample comprised men undergoing infertility assessments at a singular andrology department in north China, potentially restricting the generalizability of the findings to other regions or populations. For a comprehensive understanding, additional studies involving diverse populations were required. Thirdly, the study did not assess the effects of treatment with \u003cem\u003ePDE5\u003c/em\u003e inhibitors, despite the observed association between the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism and the risk of ED. Furthermore, this study did not assess important metabolic and hormonal parameters, such as total testosterone levels and thyroid function. Additionally, penile ultrasound examination results were not taken into account. Finally, there might have been a potential for recall bias when gathering data on the severity of ED using the IIEF-5 questionnaire. Addressing these limitations in future research will enable a more comprehensive assessment of the topic.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThe findings of this study suggest a positive association between the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism and an increased risk of severe ED. The identification of \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms could serve as valuable additional information for the clinical diagnosis of ED in routine practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCOMPETING INTERESTS\u003c/h2\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eEthics Approval and Consent to Participate:\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First Affiliated Hospital of Shandong Second Medical University of China (Approval No. 20220521-JY-001). Written informed consent was obtained from all participants prior to their inclusion in the study.\u003c/p\u003e\n\u003ch2\u003eConsent to Publish\u003c/h2\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003ch2\u003eFunding Declaration\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the grants from the Key Common Technology Research and Development Project in Hefei City, China (GJ2022SM09) and 2023 Anhui Province Clinical Key Specialty Fund.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eThe research study was designed by XF, MH, and FG. Data acquisition was contributed by XF, MH, and HZ. Data analysis was conducted by XF, MH, and FG were responsible for writing the paper. XF, MH, and FG revised the manuscript and provided comments. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the grants from the Key Common Technology Research and Development Project in Hefei City, China (GJ2022SM09) and 2023 Anhui Province Clinical Key Specialty Fund\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMcCabe MP, Sharlip ID, Atalla E, Balon R, Fisher AD, Laumann E, et al. Definitions of Sexual Dysfunctions in Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015. J. Sex. Med. 2016; 13: 135-43.\u003c/li\u003e\n\u003cli\u003eLotti F, Maggi M. Sexual dysfunction and male infertility. Nat. Rev. Urol. 2018; 15: 287-307.\u003c/li\u003e\n\u003cli\u003eBodie JA, Beeman WW, Monga M. Psychogenic erectile dysfunction. Int. J. Psychiatr. Med. 2003; 33: 273-93.\u003c/li\u003e\n\u003cli\u003eTerentes-Printzios D, Ioakeimidis N, Rokkas K, Vlachopoulos C. Interactions between erectile dysfunction, cardiovascular disease and cardiovascular drugs. Nat. Rev. Cardiol. 2022; 19: 59-74.\u003c/li\u003e\n\u003cli\u003eGur S, Alzweri L, Yilmaz-Oral D, Kaya-Sezginer E, Abdel-Mageed A, Dick B, et al. Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum. Andrology 2020; 8: 1824-33.\u003c/li\u003e\n\u003cli\u003eLiu R, Kang YL, Chen L. Activation mechanism of human soluble guanylate cyclase by stimulators and activators. Nat. Commun. 2021; 12: 10.\u003c/li\u003e\n\u003cli\u003eLombardo R, Tema G, De Nunzio C. Phosphodiesterases 5 Inhibitors and Erectile Dysfunction Recovery after Pelvic Surgery: Future Perspectives for New Drugs and New Formulations. Curr. Drug Targets 2021; 22: 31-7.\u003c/li\u003e\n\u003cli\u003eBajraktari G, Burhenne J, Bugert P, Haefeli WE, Weiss J. Cyclic guanosine monophosphate modulates accumulation of phosphodiesterase 5 inhibitors in human platelets. Biochemical Pharmacology 2017; 145: 54-63.\u003c/li\u003e\n\u003cli\u003eVan de Voorde J, Boydens C, Pauwels B, Vanden Daele L. Inhibition of Cyclic GMP Export by Multidrug Resistance Protein 4: a New Strategy to Treat Erectile Dysfunction? J. Vasc. Res. 2017; 54: 69-.\u003c/li\u003e\n\u003cli\u003eBurnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, et al. Erectile Dysfunction: AUA Guideline. The Journal of urology 2018; 200: 633-41.\u003c/li\u003e\n\u003cli\u003eChen Y, Li J, Li TY, Long JX, Liao JL, Wei GH, et al. Association between homocysteine, vitamin B\u0026lt;sub\u0026gt;12\u0026lt;/sub\u0026gt;, folic acid and erectile dysfunction: a cross-sectional study in China. BMJ Open 2019; 9: 8.\u003c/li\u003e\n\u003cli\u003eSalvi F, Sarzani R, Giorgi R, Donatelli G, Pietrucci F, Micheli A, et al. Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5). International journal of impotence research 2004; 16: 412-7.\u003c/li\u003e\n\u003cli\u003eKessler A, Sollie S, Challacombe B, Briggs K, Van Hemelrijck M. The global prevalence of erectile dysfunction: a review. BJU international 2019; 124: 587-99.\u003c/li\u003e\n\u003cli\u003eAhmed WS, Geethakumari AM, Biswas KH. Phosphodiesterase 5 (PDE5): Structure-function regulation and therapeutic applications of inhibitors. Biomedicine \u0026amp; pharmacotherapy = Biomedecine \u0026amp; pharmacotherapie 2021; 134: 111128.\u003c/li\u003e\n\u003cli\u003eGoldstein I, Goren A, Li VW, Tang WY, Hassan TA. Epidemiology Update of Erectile Dysfunction in Eight Countries with High Burden. Sexual Medicine Reviews 2020; 8: 48-58.\u003c/li\u003e\n\u003cli\u003eColson MH, Cuzin B, Faix A, Grellet L, Huyghes E. Current epidemiology of erectile dysfunction, an update. Sexologies 2018; 27: e7-e13.\u003c/li\u003e\n\u003cli\u003eWang W, Fan J, Huang G, Zhu X, Tian Y, Tan H, et al. Meta-Analysis of Prevalence of Erectile Dysfunction in Mainland China: Evidence Based on Epidemiological Surveys. Sexual medicine 2017; 5: e19-e30.\u003c/li\u003e\n\u003cli\u003eAlhomaid AM, Moin Ahmed M. Prevalence of Non-diabetic Hyperglycemia in Young Adults and Its Impact on Periodontal Health. Cureus 2024; 16: e53847.\u003c/li\u003e\n\u003cli\u003eKaltsas A, Zachariou A, Dimitriadis F, Chrisofos M, Sofikitis N. Empirical Treatments for Male Infertility: A Focus on Lifestyle Modifications and Medicines. Diseases (Basel, Switzerland) 2024; 12.\u003c/li\u003e\n\u003cli\u003eFocusing on male infertility. Nat. Rev. Urol. 2024; 21: 61-.\u003c/li\u003e\n\u003cli\u003eLiu R, Rizzo S, Whipple S, Pal N, Pineda AL, Lu M, et al. Evaluating eligibility criteria of oncology trials using real-world data and AI. Nature 2021; 592: 629-33.\u003c/li\u003e\n\u003cli\u003eHu K, Zhao L, Zhou Q, Mei F, Gao Q, Chen F, et al. Inconsistencies in study eligibility criteria are common between non-Cochrane systematic reviews and their protocols registered in PROSPERO. Research synthesis methods 2021; 12: 394-405.\u003c/li\u003e\n\u003cli\u003eLi JZ, Maguire TA, Zou KH, Lee LJ, Donde SS, Taylor DG. Prevalence, Comorbidities, and Risk Factors of Erectile Dysfunction: Results from a Prospective Real-World Study in the United Kingdom. International journal of clinical practice 2022; 2022: 5229702.\u003c/li\u003e\n\u003cli\u003eFoulkes L, Blakemore S-J. Studying individual differences in human adolescent brain development. Nature Neuroscience 2018; 21: 315-23.\u003c/li\u003e\n\u003cli\u003eTabor HK, Risch NJ, Myers RM. Candidate-gene approaches for studying complex genetic traits: practical considerations. Nature Reviews Genetics 2002; 3: 391-7.\u003c/li\u003e\n\u003cli\u003eMa Q, lv J, Huang K, Guo H, Yang W, Luo W, et al. Endothelial nitric oxide synthase gene G894T polymorphism and risk assessment for pregnancy-induced hypertension: evidence from 11\u0026thinsp;700 subjects. Hypertension Research 2016; 39: 899-906.\u003c/li\u003e\n\u003cli\u003eKumari N, Yadav A, Ahirwar R, Sagar SK, Mondal PR. Angiotensin converting enzyme (ACE) insertion / deletion (I/D) polymorphism and its association with cardiovascular adversities \u0026ndash; A systematic review. Human Gene 2022; 34: 201117.\u003c/li\u003e\n\u003cli\u003eLin CJ, Chang YC, Cheng TY, Lo K, Liu SJ, Yeh TL. The association between metabolically healthy obesity and risk of cancer: A systematic review and meta-analysis of prospective cohort studies. Obesity reviews : an official journal of the International Association for the Study of Obesity 2020; 21: e13049.\u003c/li\u003e\n\u003cli\u003eNehra A. Erectile Dysfunction and Cardiovascular Disease: Efficacy and Safety of Phosphodiesterase Type 5 Inhibitors in Men With Both Conditions. Mayo Clinic Proceedings 2009; 84: 139-48.\u003c/li\u003e\n\u003cli\u003eMostafa T, Hassan A, Alghobary MF, Abdelrahman SH. Effect of Genetic Polymorphism on the Response to PDE5 Inhibitors in Patients With Erectile Dysfunction: A Systematic Review and a Critical Appraisal. Sexual Medicine Reviews 2020; 8: 573-85.\u003c/li\u003e\n\u003cli\u003eZhang Z, Huang W, Huang D, Xu Z, Xie Q, Tan X, et al. Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription. Communications Biology 2025; 8: 85.\u003c/li\u003e\n\u003cli\u003eKolontarev K, Govorov A, Kasyan G, Priymak D, Pushkar D. Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors. Central European journal of urology 2016; 69: 398-403.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Erectile dysfunction (ED), PDE5 gene polymorphism, rs3806808 locus, Genetic susceptibility, Severe ED risk","lastPublishedDoi":"10.21203/rs.3.rs-6780139/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6780139/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eInherited factors had been demonstrated to play important roles in the onset of erectile dysfunction (ED). Nevertheless, the impact of phosphodiesterase 5 (\u003cem\u003ePDE5\u003c/em\u003e) gene mutations on the susceptibility to ED remained uncertain. For this study, 627 patients were enrolled and evaluated for ED by utilizing the International Index of Erectile Function-5. The \u003cem\u003ePDE5\u003c/em\u003e mutation was analyzed through fluorescence-based polymerase chain reaction (PCR). There were no notable variations among the genotypic distribution of the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism (TT, GT, and GG) at rs3806808 locus observed between individuals in the non-ED and ED cohorts. Furthermore, in both crude and adjusted binary logistic regression models, the presence of the \u003cem\u003ePDE5\u003c/em\u003e gene polymorphism did not demonstrate a significant association with the risk of ED. Interestingly, a significantly higher prevalence of the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism at the rs3806808 locus was detected in cases of moderate and severe ED (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). The link between the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism and severe ED was supported by logistic regression analysis, even after considering potential confounding factors (odds ratio [OR]\u0026thinsp;=\u0026thinsp;2.35, 95% confidence interval [CI]: 1.04\u0026ndash;5.39, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). The study findings suggested a direct link between the presence of the \u003cem\u003ePDE5\u003c/em\u003e TT polymorphism and a heightened risk of severe ED. Identification of \u003cem\u003ePDE5\u003c/em\u003e gene polymorphisms could offer additional insights for clinicians in the routine diagnosis of patients with ED.\u003c/p\u003e","manuscriptTitle":"Study on correlation between gene polymorphism of PDE5 rs3806808 locus and erectile dysfunction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-07 09:48:16","doi":"10.21203/rs.3.rs-6780139/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"645d2226-da64-4a30-a9d4-32e489281e54","owner":[],"postedDate":"July 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-14T12:55:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-07 09:48:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6780139","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6780139","identity":"rs-6780139","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}