The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients

OBJECTIVE — Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (45TG and 276GT) have been associated with low circulating adiponectin levels, insulin resistance, and type 2 diabetes. We investigated whether these genetic markers are determinants of coronary artery disease (CAD) in type 2 diabetic patients. RESEARCH DESIGN AND METHODS — A total of 376 consecutive type 2 diabetic patients were studied: 142 case subjects with coronary stenosis 50% or previous myocardial infarction and 234 control subjects with no symptoms, no electrocardiogram (ECG) signs of myocardial ischemia, and a normal ECG stress test (n 189) and/or (n 45) with coronary stenosis 50%. RESULTS— NoassociationwithCADwasobservedforthe45SNP(P0.48).Bycontrast, a significant association was observed for the 276 SNP, with T/T homozygotes having a lower risk of CAD than carriers of other genotypes (adjusted odds ratio [OR] 0.13 [95% CI 0.037– 0.46], P 0.002). A similarly protective effect of the 276 T/T genotype was observed in 110 case and 45 control subjects for whom the CAD status had been determined by angiography (0.04 [0.006 – 0.30], P 0.002). Serum adiponectin, although clearly related to several features of the proatherogenic/insulin- resistant phenotype, was not different between control subjects and CAD patients (26 17 vs. 25 13 g/ml). CONCLUSIONS — In conclusion, the 276 GT polymorphism is a determinant of CAD risk in type 2 diabetic patients. This marker may assist in the identification of diabetic individuals at especially high risk of CAD, so that preventive programs can be targeted at these subjects.