CYP1A1, GSTM1 and GSTT1 genetic polymorphism is associated with susceptibility to polycystic ovaries in South Indian women.
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 CYP1A1 (T6235C), GSTM1 and GSTT1 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 GSTM1 and GSTT1 null genotypes in PCO cases and healthy controls. However, CYP1A1 Msp I homozygous mutants were strongly associated (P = 0.0139) with increased susceptibility to PCO. Three genotype combinations, CYP1A1 (mt/mt) with GSTM1 [-] and GSTT1 [-], CYP1A1 (wt/mt) with GSTM1 [-] and GSTT1 [-] and CYP1A1 (mt/mt) with GSTM1 [-], GSTT1 [+], were also observed in women with PCO. In conclusion, the presence of hyperinducible CYP1A1 (T6235C) mutant genotype and its mutants in combination with GSTM1 and GSTT1 null genotypes might cause an imbalance between phase I and phase II enzymes, and therefore may represent a risk factor for PCO.
Babu
K Arvind
KA
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad-500007, AP, India.
Rao
K Lakshmi
KL
Kanakavalli
M K
MK
Suryanarayana
V V
VV
Deenadayal
Mamata
M
Singh
Lalji
L
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D009154:Mutation; D016017:Odds Ratio; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1