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

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

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.

Abbreviations: CVD, cardiovascular disease; MI, myocardial infarction; SNP, single nucleotide polymorphism

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