Genetic Variation at the Adiponectin Locus and Risk of Type 2 Diabetes in Women

Previous data suggesting that polymorphisms in the adiponectin gene were associated with insulin resistance or type 2 diabetes have been inconsistent. We assessed the relationship between five common haplotype-tagging single nucleotide polymorphisms (SNPs) in the adiponectin gene (−11365C>G, −4034A>C, −3964A>G, +45T>G, and +276G>T), haplotypes defined by these SNPs, and the risk of type 2 diabetes by conducting a nested case-control study of 642 incident cases of type 2 diabetes and 995 matching control subjects in the Nurses’ Health Study. Overall, we did not observe significant differences in genotype or allele frequencies for the five SNPs between the case and control subjects. After adjustment for diabetes risk factors, the −4034 C/C genotype was associated with a reduced risk of diabetes (odds ratio [OR] compared with the A/A genotype = 0.70, 95% CI 0.50–0.99, P = 0.04). In subgroup analyses, the +276 genotype was significantly associated with diabetes risk only among subjects with peroxisome proliferator-activated receptor-γ (PPARγ) variant 12Ala allele (OR comparing +276 T alleles with the G/G genotype = 1.69, 1.04–2.75, P = 0.035) or among obese subjects (1.46, 1.03–2.08, P = 0.03). These data suggest a potential interaction between the adiponectin genotype and PPARγ genotype or obesity, but these analyses should be considered exploratory and require further investigation in larger studies.