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A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus

Hayek, T; Stephens, JW; Hubbart, CS; Acharya, J; Caslake, MJ; Hawe, E; ... Humphries, SE; + view all (2006) A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus. ATHEROSCLEROSIS , 184 (2) 404 - 412. 10.1016/j.atherosclerosis.2005.05.017.

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Abstract

Introduction: Glutathione S transferases (GST) are enzymes responsible for the metabolism of numerous xenobiotics and play a major cellular antioxidant role. Our aim was firstly, to examine the association between the GST M1/GST mu-1 (GSTM 1) and GST T1/GST theta-1 (GSTT1) gene variants with markers of oxidative stress and inflammation in diabetic patients, and secondly to examine the association and potential interaction between these variants and cigarette smoking.Methods: Seven hundred and seventy-three Caucasian subjects with diabetes and 2592 Caucasian non-diabetic subjects were successfully genotyped. Plasma total antioxidant status, C-reactive protein (CRP), oxidized-LDL (Ox-LDL) and LDL-mean/peak particle diameter were recorded in the diabetes sample.Results: No association was seen between genotype and cardiovascular disease (CVD) risk. In the diabetic subjects, GSTT1-1 compared to GSTT1-0 subjects had significantly higher CRP (p = 0.001), Ox-LDL (p = 0.004) and smaller LDL particles (p = 0.01). In subjects without CVD, there was a significant interaction between the GSTT1-1 variant and smoking in determining Ox-LDL (p = 0.04). Furthermore, CVD risk was higher in smokers compared to non-smokers with GSTT1-1. No significant associations were observed by GSTM1. Within the nondiabetic sample, no association was observed between genotype and prospective coronary heart disease (CHID) risk. Of note, the frequency of the GSTT1-1 variant was significantly lower in the diabetes subjects compared to the non-diabetic sample (p = 0.01).Conclusions: This study demonstrates an association between the GSTT1-1 variant and markers of inflammation and lipid peroxidation. Furthermore this variant interacts with smoking to increase lipid peroxidation. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Type:Article
Title:A common variant in the glutathione S transferase gene is associated with elevated markers of inflammation and lipid peroxidation in subjects with diabetes mellitus
DOI:10.1016/j.atherosclerosis.2005.05.017
Keywords:glutathione S transferase, oxidative stress, oxidized-LDL, CVD, diabetes mellitus, inflammation, CORONARY-ARTERY-DISEASE, CIGARETTE-SMOKING, ENDOTHELIAL DYSFUNCTION, MOLECULAR EPIDEMIOLOGY, BLADDER-CANCER, HEART-DISEASE, LUNG-CANCER, M1 GSTM1, RISK, ATHEROSCLEROSIS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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