Association of CYPIAI gene polymorphism with recurrent pregnancy loss in the South Indian population

Polymorphic variants in the phase I enzyme, cytochrome P450 gene, may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes, may result in impaired detoxification. Alterations in the activities of phase I drug metabolizing enzymes and phase II detoxification enzymes may cause abnormal functioning and formation of follicular cysts in the ovaries and thus causing an imbalance in the hormone profiles. This study aimed to investigate the relationship between genetic polymorphisms of CYP1Al (T6235C), GSTMJ and GSTTI in South Indian women with polycystic ovaries (PCO) using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of variants of these genes were studied in 180 women with confirmed PCO and in 72 healthy fertile women with successful pregnancy record. No significant difference was found between the frequencies of GSTMI and GSTTJ null genotypes in PCO cases and healthy controls. However, CYPIAI Msp I homozygous mutants were strongly associated (P = 0.0139) with increased susceptibility to PCO. Three genotype combinations, CYPIAJ(mt!mt) with GSTMI[-] and GSTTI[-]. CYPJAJ(wtlmt) with GSTMI[-] and GSTTJ[-] and CYPIAJ(mt!mt) with GSTMJ[-], GSTTl[+]. were also observed in women with PCO. In conclusion, the presence of hyperinducible CYP JAJ (T6235C) mutant genotype and its mutants in combination with GSTMI and GSTTJ null genotypes might cause an imbalance between phase I and phase II enzymes, and therefore may represent a risk factor for PCO.