Hayek, T., Stephens, J.W., Hubbart, C.S., Acharya, J., Caslake, M.J., Hawe, E., Miller, G.J., Hurel, S.J. and Humphries, S.E. (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), pp. 404-412. (doi: 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 (GSTM1) 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 non-diabetic sample, no association was observed between genotype and prospective coronary heart disease (CHD) 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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Caslake, Professor Muriel |
Authors: | Hayek, T., Stephens, J.W., Hubbart, C.S., Acharya, J., Caslake, M.J., Hawe, E., Miller, G.J., Hurel, S.J., and Humphries, S.E. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences |
Journal Name: | Atherosclerosis |
Publisher: | Elsevier Ireland Ltd |
ISSN: | 0021-9150 |
ISSN (Online): | 1879-1484 |
Published Online: | 05 July 2005 |
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