The +276 Polymorphism of the APM1 Gene, Plasma Adiponectin Concentration, and Cardiovascular Risk in Diabetic Men

The +276 Polymorphism of the APM1 Gene, Plasma Adiponectin Concentration, and Cardiovascular Risk in Diabetic Men Lu Qi 1 2 , Tricia Li 1 , Eric Rimm 1 2 3 , Cuilin Zhang 1 2 , Nader Rifai 4 , David Hunter 1 2 3 , Alessandro Doria 5 and Frank B. Hu 1 2 3 1 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 2 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 3 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 4 Department of Laboratory Medicine, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 5 Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts Address correspondence and reprint requests to Dr. Lu Qi, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. E-mail: nhlqi{at}channing.harvard.edu Abstract Recently, the genetic variability at adiponectin locus ( APM1 ) was associated with cardiovascular risk in patients with type 2 diabetes. We sought to examine the associations of five variants of APM1 gene (C-11365G, A-4034C, A-3964G, T45G, and G276T) with the risk of cardiovascular diseases (CVDs) in a larger cohort of diabetic patients. Of 879 diabetic men from the Health Professionals Follow-up Study, 239 participants developed coronary heart disease or stroke during 14 years of follow-up and 640 CVD-negative subjects were used as control subjects. The risk of CVD was significantly lower in TT homozygotes at locus +276 than in other genotypes under a recessive inheritance model after adjusting for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbA 1c , and history of hypertension or hypercholesterolemia (odds ratio 0.38 [95% CI 0.18–0.79]; P = 0.009). In the CVD-negative control subjects, the allele 276T was associated with significantly higher plasma adiponectin levels in a dose-dependent pattern (GG 14.8, GT 16.2, and TT 18.8 μg/ml) after adjusting for age, BMI, and other variables ( P for trend = 0.0019). In conclusion, our study showed significant associations between APM1 G276T and decreased CVD risk and increased plasma adiponectin levels in diabetic men. CVD, cardiovascular disease MI, myocardial infarction SNP, single nucleotide polymorphism Footnotes Accepted February 17, 2005. Received November 15, 2004. DIABETES