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
- 12 October 2021
- journal article
- research article
- Published by Springer Nature in Reproductive Sciences
- Vol. 29 (6) , 1790-1800
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-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.Keywords
Funding Information
- National Natural Science Foundation of China (81370681)
- Program for Changjiang Scholars and Innovative Research Team in University, Ministry of Education (IRT0935)
This publication has 47 references indexed in Scilit:
- Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysisCanadian Medical Association Journal, 2012
- Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop GroupFertility and Sterility, 2012
- Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitusBMC Medical Genetics, 2011
- Interaction of GAG trinucleotide repeat and C − 129 T polymorphisms impairs expression of the glutamate–cysteine ligase catalytic subunit geneFree Radical Biology and Medicine, 2011
- Association of polymorphisms of glutamate‐cystein ligase and microsomal triglyceride transfer protein genes in non‐alcoholic fatty liver diseaseJournal of Gastroenterology and Hepatology, 2010
- Combined effect of oxidative stress-related gene polymorphisms on atherosclerosisBiochemical and Biophysical Research Communications, 2009
- Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligaseMolecular Aspects of Medicine, 2009
- Regulation of glutathione synthesisMolecular Aspects of Medicine, 2009
- Glutamate Cysteine Ligase Catalytic Subunit Promoter Polymorphisms and Associations with Type 1 Diabetes Age-at-onset and GAD65 Autoantibody LevelsExperimental and Clinical Endocrinology & Diabetes, 2007
- C–588T polymorphism of the human glutamate-cysteine ligase modifier subunit gene is not associated with the risk and extent of ischemic heart disease in a German cohortClinical Chemistry and Laboratory Medicine (CCLM), 2007