The +276G/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 (+45>G and +276G>T) 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 electrogram (ECG) signs of myocardial ischemia, and a normal ECG stress test (n = 189) and/or (n = 45) with coronary stenosis less than or equal to50%. RESULTS- No association with CAD was observed for the +45 SNP (P = 0.48). By contrast, 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) 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 mug/ml). CONCLUSIONS- In conclusion, the +276 G>T 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.