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


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.
Stephens
Jeffrey W
JW
Diabetes Research Group, The Medical School, Swansea University, Grove Building Swansea University, Swansea SA2 8PP, UK. j.w.stephens@swansea.ac.uk
Dhamrait
Sukhbir S
SS
Mani
Ali R
AR
Acharya
Jayshree
J
Moore
Kevin
K
Hurel
Steven J
SJ
Humphries
Steve E
SE
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003327:Coronary Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000097:blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D000071246:Uncoupling Protein 2
D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2