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

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-129 T) and the modifier subunit (GCLM C-588 T) 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-129 T 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 -129 T 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 -129 T 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-129 T and its combination with the CC genotype of SNP GCLM C-588 T are associated with decreased risk of HA-PCOS in Chinese women.