Angiotensin-converting Enzyme Insertion/Deletion Polymorphism Distribution in the North Indian Population of Jammu and Kashmir and Its Positive Correlation with Male Infertility: A Case Control Study.

Abstract

Background: A precise balance among angiotensin-converting enzyme (ACE), angiotensin-II (Ang-II) and Ang-II type 1 receptor is essential for spermatogenesis. Any alteration in this balance can potentially lead to infertility.

Aim: To study the potential association of the ACE Insertion (I)/deletion (D) polymorphism with male infertility in the North Indian population of Jammu and Kashmir.

Settings and design: This case-control genetic association study was conducted on 362 subjects in the North Indian population of Jammu and Kashmir. All participants provided informed consent, and the study was approved by the institutional human ethics committee.

Materials and methods: DNA was extracted from blood using a kit (Qiagen Pvt. Ltd., Germany). The primer sequence was taken from the literature. Ready-to-use PCR mix from Takara Bioscience was used to genotype the ACE I/D polymorphism in 162 infertile men and 200 healthy controls.

Statistical analysis used: Logistic regression, t-test and Chi-square were used to perform the statistical comparisons between cases and controls using SPSS v25.0 and other online statistical tools.

Results: The D allele frequency in combined cases was significantly higher than in the control group, with values of 0.52 compared to 0.34 (P = 0.04). Similarly, the genotypic frequency distribution between cases and controls was significantly different, with cases having a higher prevalence of the DD genotype than controls (27.7% vs. 9.5%, respectively). Our data suggest that men with the DD genotype are approximately five times more likely to experience infertility than those with the II genotype in the study population, with an odds ratio (OR) of 4.94 (95% confidence interval [CI] 2.45-9.97). Furthermore, infertile men with the DD genotype exhibited lower sperm count (54.2 ± 13.1 million/mL) and progressive motility (41.2 ± 12.8%) compared to the II carriers (sperm counts 59.1 ± 13.2 million/mL and progressive motility 47.7 ± 11.5%). When analysed separately, only asthenoteratozoospermic and idiopathic cases showed a highly significant association with the DD genotype when compared with the control group (OR 4.7 [95% CI 2.09-10.34] and OR 6.3 [95% CI 2.79-14.90], respectively).

Conclusion: Our study is the first report linking the ACE I/D polymorphism to male infertility in any Indian population. The D allele appears to pose a greater risk for male infertility in the study population, particularly for asthenoteratozoospermic and idiopathic infertility.