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Interaction between the uncoupling protein 2 -866G>A gene variant and cigarette smoking to increase oxidative stress in subjects with diabetes.

Stephens JW, Dhamrait SS, Mani AR, Acharya J, Moore K, Hurel SJ, Humphries SE

Diabetes Research Group, The Medical School, Swansea University, Grove Building Swansea University, Swansea SA2 8PP, UK. j.w.stephens@swansea.ac.uk

BACKGROUND AND AIMS: Increased oxidative stress is associated with coronary heart disease (CHD). The mitochondrial uncoupling protein-2 (UCP2) negatively regulates reactive oxygen species generation. We have observed that a common variant (-866G>A) in the promoter region of UCP2 is associated with increased CHD risk in healthy men and increased oxidative stress in diabetic men with CHD. The aim of the current study was to test the hypothesis that this variant might interact with smoking (an environmental stress) to influence plasma markers of oxidative stress. METHODS AND RESULTS: Amongst 453 Caucasian diabetic men there was a significant interaction (p=0.001) between genotype and smoking in determining plasma Total AntiOxidant Status (TAOS). Current smokers with the -866AA genotype had the lowest TAOS (indicating higher oxidative stress) of all subjects (AA vs. GG: 32.00+/-17.4% vs. 45.8+/-12.6%, p=0.04). In a sub-sample of 20 subjects (10 GG, 10 AA) matched for baseline characteristics, plasma markers of oxidative stress in current smokers were significantly higher in AA compared to GG subjects (TAOS 36.8+/-9.5% vs. 51.4+/-9.5%, p=0.04; F(2)-isoprostanes 1133.6+/-701.2 pg ml(-1) vs. 500.8+/-64.7 pg ml(-1), p=0.04). CONCLUSIONS: This study demonstrates an interaction between the UCP2 -866G>A variant and smoking to increase oxidative stress in vivo.

Published 25 December 2007 in Nutr Metab Cardiovasc Dis, 18(1): 7-14.
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