A49T, R227Q and TA repeat polymorphism of steroid 5 alpha-reductase type II gene and Hypospadias risk in North Indian children

BACKGROUND/AIMS: 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 functional polymorphisms of SRD5A2 gene in relation to hypospadias. METHODS: We examined DNA samples of 96 cases and 105 controls for SRD5A2-A49T, R227Q and TA repeat gene polymorphisms. RESULT: Absence of 49T locus and 227Q locus was observed in the present study. At the (TA) n repeat site, TA (0) allele was observed to be the most common allele in both cases (91.7%) and controls (90%). TA (9/9) genotype exhibited an odds ratio of 3.03 (95% C.I. = 0.18–50.14, p = 0) with respect to only middle phenotypes. Analysis of the demographic data depicted the agricultural background aspect of the parents of the cases. 72.27% of the cases (affected with Hypospadias) have parents having agriculture as a primary occupation. CONCLUSION: As longer TA repeats are associated with lower enzymatic activity and lower DHT levels as reported among Caucasians, this polymorphism may have an effect (rather small) in predisposing the population of the present study to the risk of Hypospadias of lesser severity. Due to small sample size, the 3.03 O.R. is not significant and a larger sample is needed to validate the results. Large scale screening of Hypospadias and other 46 X,Y disorders of sexual development is needed especially in India, where the majority of the population is from agricultural background. The results of the present study are likely to assist the health planners to initiate screening of Hypospadias among the farmer community to combat the risk of Hypospadias.