The common G-866A polymorphism of the UCP2 gene and survival in diabetic patients following myocardial infarction.
BACKGROUND
A variant in the promoter of the human uncoupling protein 2 (UCP2) gene, the G-866A polymorphism, has been associated with future risk of coronary heart disease events, in those devoid of traditional risk factors and in those suffering from diabetes. We thus examined the impact of the G-866A polymorphism on 5-year survival in a cohort of 901 post-myocardial infarction patients, and the impact of type-2 diabetes on this relationship. The association of UCP2 with baseline biochemical and hormonal measurements, including levels of the inflammatory marker myeloperoxidase, was also examined.


METHODS
UCP2 G-866A genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Myeloperoxidase levels were measured in plasma samples taken from 419 cohort patients 24-96 hours after admission.


RESULTS
Genotypes were obtained for 901 patients with genotype frequencies AA 15.5%, GA 45.5%, and GG 39.0%. Genotype was not associated with survival in the overall cohort (mortality: AA 15.6%, GA 16.8%, GG 19.4%, p = 0.541). However, amongst diabetics, AA and GA genotype groups had significantly worse survival than GG diabetic patients (p < 0.05) with an attributable risk of 23.3% and 18.7% for those of AA and GA genotype respectively. Multivariate analysis using a Cox proportional hazards model confirmed that the interaction of diabetes with genotype was significantly predictive of survival (p = 0.031). In the cohort's diabetic subgroup AA/GA patients had higher myeloperoxidase levels than their GG counterparts (GA/AA, n = 51, 63.9 +/- 5.23; GG, n = 34, 49.1 +/- 3.72 ng/ml, p = 0.041). Further analysis showed that this phenomenon was confined to male patients (GA/AA, n = 36, 64.3 +/- 6.23; GG, n = 29, 44.9 +/- 3.72 ng/ml, p = 0.015).


CONCLUSIONS
Diabetic patients in this post-myocardial infarction cohort with UCP2 -866 AA/GA genotype have poorer survival and higher myeloperoxidase levels than their GG counterparts.
Palmer
Barry R
BR
Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. barry.palmer@otago.ac.nz
Devereaux
Courtney L
CL
Dhamrait
Sukhbir S
SS
Mocatta
Tessa J
TJ
Pilbrow
Anna P
AP
Frampton
Chris M
CM
Skelton
Lorraine
L
Yandle
Tim G
TG
Winterbourn
Christine C
CC
Richards
A Mark
AM
Montgomery
Hugh E
HE
Cameron
Vicky A
VA
D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D009195:Peroxidase / Q000096:biosynthesis; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015996:Survival Rate / Q000639:trends; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D009195:Peroxidase