Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly

BACKGROUND: Genetic variations of the human adiponectin gene are associated with metabolic phenotypes, including obesity, insulin sensitivity, and diabetes. However, these associations have not been examined in an elderly population. OBJECTIVE: The objective of the study was to investigate whether the genetic variants of adiponectin are associated with any metabolic phenotype in the elderly. DESIGN: In a population-based, case-control genetic association study, a total of 1438 subjects >65 y old were recruited from the community. The phenotypes of the metabolic syndrome (MetS) were measured. Four single-nucleotide polymorphisms (SNP) were genotyped by mass spectrometry. RESULTS: The G allele of SNP276 in intron 2 was associated with a reduced risk of obesity, MetS, and diabetes mellitus. The GT genotype relative to the GG genotype had an age- and sex-adjusted odds ratio of 1.32 for obesity [body mass index (BMI; in kg/m(2)) >or= 25; P = 0.014] and of 1.33 (P = 0.011) and 1.47 (P = 0.001) for MetS according to modified National Cholesterol Education Program and International Diabetes Federation criteria, respectively. The age-, sex-, and BMI-adjusted odds ratio of diabetes mellitus for the GT and TT genotypes relative to the GG genotype were 1.28 (P = 0.042) and 1.72 (P = 0.013), respectively, and there was an obvious dosage effect (P for trend = 0.004). In linear regression after adjustment for age, sex, and BMI, the GT and TT genotypes were associated with fasting plasma glucose concentrations 5.2 and 11.1 mg/dL higher, respectively, than those of the GG genotype. CONCLUSIONS: Genetic variation of the adiponectin gene is associated with obesity, MetS, and diabetes mellitus in the elderly. The genetic effect on diabetes mellitus is partially independent of BMI.