Association of genetic polymorphisms in SOD2, SOD3, GPX3, and GSTT1 with hypertriglyceridemia and low HDL-C level in subjects with high risk of coronary artery disease

Abstract

Background. Oxidative stress modulates insulin resistant-related atherogenic dyslipidemia: hypertriglyceridemia (HTG) and low high-density lipoprotein cholesterol (HDL-C) level. Gene polymorphisms in superoxide dismutase (SOD2 and SOD3), glutathione peroxidase-3 (GPX3), and glutathione S-transferase theta-1 (GSTT1) may enable oxidative stress-related lipid abnormalities and severity of coronary atherosclerosis. The present study investigated the associations of antioxidant-related gene polymorphisms with atherogenic dyslipidemia and atherosclerotic severity in subjects with high risk of coronary artery disease (CAD). Methods. Study population comprises of 396 subjects with high risk of CAD. Gene polymorphisms: SOD2 rs4880, SOD3 rs2536512 and rs2855262, GPX rs3828599, and GSTT1 (deletion) were evaluated the associations with HTG, low HDL-C, high TG/HDL-C ratio, and severity of coronary atherosclerosis. Results. SOD2 rs4880-CC, SOD3 rs2536512-AA, rs2855262-CC, and GPX3 rs3828599- AA, but not GSTT1-/- individually increased risk of HTG combined with low HDL-C level. With a combination of five risk-genotypes as a genetic risk score (GRS), GRS ≥ 6 increased risks of low HDL-C, high TG/HDL-C ratio, and HTG combined with low HDL-C, comparing with GRS 0-2 [respective adjusted ORs (95% CI) = 2.70 (1.24-5.85), 3.11 (1.55-6.23), and 5.73 (2.22-14.77)]. Gene polymorphisms, though, were not directly associated with severity of coronary atherosclerosis; high TG/HDL-C ratio was associated with coronary atherosclerotic severity [OR = 2.26 (95% CI [1.17-4.34])]. Conclusion. Combined polymorphisms in antioxidant-related genes increased the risk of dyslipidemia related to atherosclerotic severity, suggesting the combined antioxidantrelated gene polymorphisms as predictor of atherogenic dyslipidemia.