Association of polymorphism c.-124G>A and c.-16 C>T in the promoter region of human INHA gene with altered sperm parameters; A pilot study

Abstract

Objective: The objective of this was to demonstrate the association of Inhibin alpha (INH alpha) c.-124G>A and INH alpha-c.-16 C>T polymorphisms with altered sperm parameters in a selected male population of Karachi, Pakistan. Study Design & Settings: In this pilot study, male subjects were stratified on the basis of the WHO criteria for altered sperm parameters; 83 (cases-altered sperm parameters) and 30 (controls-normal sperm parameters) subjects were included for analysis of INH alpha-c.124G>A polymorphism and 88 (cases) and 38 (controls) were analysed for INH alpha - c-16 C>T polymorphism. Genotyping of INH alpha-c.-124G>A and INH alpha-c.-16 C>T was performed by PCR-RFLP, genotype distribution in Hardy-Weinberg equilibrium was evaluated by binary logistic regression model. Results: For the c.-124G>A polymorphism in INH alpha gene, frequency of the three major genotypes in controls was: GG: 80.0%, GA: 20.0% and AA: 0% and in cases was: GG: 59.0%, GA: 30.2% and AA: 10.8%. The GG genotype was significantly associated with male infertility (P < .045, OR = 2.776, 95% CI = 1.025-7.513) while the GA genotype was not significantly associated with infertility (P < .290 OR = 0.580, 95% CI = 0.211-1.593). Frequency of mutant AA genotype was 10.8% in cases (altered sperm parameters) and absent (0%) in normal sperm parameter (controls). The frequencies of three major genotypes CC, CT and TT did not show any significant difference between cases and controls (P > .05). Conclusion: The results from our study exhibited a significant association of c.-124G>A polymorphism in the INH alpha gene promoter region with male infertility in the Pakistani population. A significant association of c.-16 C>T polymorphism with male infertility, however, was not observed. Further large-scale studies should be conducted to confirm this association.