Hypospadias risk and polymorphism in SRD5A2 and CYP17 genes: case-control study among Indian children

Purpose: Hypospadias is a common congenital error of genital development, the frequency of which is increasing. As androgens have a significant role in the development of the male urethra, we sought to investigate the association between 2 functional polymorphisms, CYP17-A1/A2 and SRD5A2-V89L, which are involved in the biosynthesis of testosterone and dihydrotestosterone, respectively, in relation to hypospadias.

Materials and methods: We examined DNA samples of 80 cases and 100 controls for SRD5A2-V89L and CYP17-A1/A2 gene polymorphisms. Information pertaining to family history, preoperative position of the urethral meatus and parental occupations along with maternal reproductive profile were collected for cases and controls.

Results: Genotyping of 80 cases and 100 controls revealed a significant association between V89L polymorphism and hypospadias (OR 2.4, 95% CI 1.2-4.6, p <0.05). When analyzing the risk of hypospadias based on grade, genotypic distribution of SRD5A2-LL genotype differed significantly between severe forms and controls, with an odds ratio of 3.6 (95% CI 1.2-10.0, p = 0.02). Of affected children 71.25% had parents from a rural background, with agriculture as the primary occupation. A statistically significant association was observed for the LL genotype (OR 4.6, 95% CI 1.7-12.29, p <0.05) between children with parents having an agricultural background (likely exposed to pesticides) and controls with no such exposure. CYP17-A1/A2 genotypes did not show any significant results.

Conclusions: V89L polymorphism of the SRD5A2 gene is a strong determinant of hypospadias risk among children of Indian origin. However, our results suggest that the presence of leucine allele, especially among agriculturalists, may increase the propensity of having a child with hypospadias.