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.

Nisa Decharatchakul,Nongnuch Settasatian,Nantarat Komanasin,Chatri Settasatian,Upa Kukongviriyapan,Vichai Senthong,Phongsak Intharaphet

doi:10.7717/peerj.7407

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.

Nisa Decharatchakul, Nongnuch Settasatian + Show 5 more

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https://doi.org/10.7717/peerj.7407

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Journal: PeerJ	Publication Date: Aug 1, 2019
Citations: 18	License type: CC BY 4.0

Affiliation: Khon Kaen University

Abstract

BackgroundOxidative 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).MethodsStudy 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.ResultsSOD2 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])].ConclusionCombined polymorphisms in antioxidant-related genes increased the risk of dyslipidemia related to atherosclerotic severity, suggesting the combined antioxidant-related gene polymorphisms as predictor of atherogenic dyslipidemia.

Highlights

Atherosclerosis is the major cause of coronary artery disease (CAD)
The study population was first divided into two groups based on the degree of coronary atherosclerosis, using Gensini score (GS) 32 as the cut-off point, and Gender: Male, n (%) Female, n (%) Smoking status; n (%) High TG/high-density lipoprotein cholesterol (HDL-C) (≥3; unit mg/dL) High TG/HDL-C (≥3.7; unit mg/dL) Metabolic syndrome; n (%) CAD; n (%) Age Gensini score HOMA-insulin resistance (IR) systolic blood pressure (SBP) diastolic blood pressure (DBP) body mass index (BMI) Waist/hip ratio fasting blood sugar (FBS) TC TG HDL-C LDL-C TG/HDL-C TG/HDL-C high-sensitivity C-reactive protein (hsCRP)
We have demonstrated that four polymorphisms in antioxidant genes (SOD2 rs4880, SOD3 rs2536512 and rs2855262, and glutathione peroxidase-3 (GPX3) rs3828599) are independently associated with combined HTG and low HDL-C in subjects with high risk of CAD

Summary

Introduction

Atherosclerosis is the major cause of coronary artery disease (CAD). Atherogenesis is a complex interplay of abnormal plasma lipid level (dyslipidemia), oxidative stress, and dysfunctional endothelial cells. IR enables adipocyte lipolysis that increases hepatic in-flux of free fatty acids (FFA), by which it induces hepatic TG synthesis This leads to increased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) and results in elevated blood TG level (Welty, 2013). 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). 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. 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

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Results

Conclusion