Association of Polymorphisms of Glutamate Cysteine Ligase Genes GCLC C-129T and GCLM C-588T with Risk of Polycystic Ovary Syndrome in Chinese Women.

Abstract

Polycystic ovary syndrome (PCOS) is generally considered a multifactorial disease caused by interactions between multiple susceptible genes and environmental factors. Glutamate cysteine ligase (GCL) is the rate-limiting enzyme in glutathione biosynthesis. This study examined the relationship between single nucleotide polymorphisms (SNPs) in the GCL catalytic subunit (GCLC C-129T) and the modifier subunit (GCLM C-588T) and PCOS. The two SNPs were genotyped in 1017 PCOS patients and 793 control women. Clinical, metabolic, hormonal, and oxidative stress parameters were also assessed. The frequencies of the CT + TT genotypes (21.6% vs. 27.7%) and T allele (11.5% vs. 14.7%) of SNP GCLC C-129T were significantly lower in hyperandrogenism (HA)-PCOS patients than in control women. Logistic regression analysis revealed that the relative hazard of HA-PCOS was lower in individuals with the -129T allele (CT + TT genotypes) than in those with the CC genotype (OR = 0.723, 95% CI: 0.571-0.915, P = 0.007). When using the GCLC-CC/GCLM-CC combined genotype as the reference category, the GCLC-CT + TT/GCLM-CC combined genotype was a protective factor for PCOS with HA (OR = 0.743, 95% CI: 0.566-0.976, P = 0.033). HA-PCOS patients with the -129T allele had lower waist circumference, waist-to-hip ratio, and body mass index (BMI) and lower fasting insulin concentration and homeostatic model assessment of insulin resistance after correcting for age and BMI (P < 0.05). The T allele of SNP GCLC C-129T and its combination with the CC genotype of SNP GCLM C-588T are associated with decreased risk of HA-PCOS in Chinese women.