Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women.

OBJECTIVE: We explored potential associations of two single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; +45T>G, rs2241766 and +276G>T, rs1501299) with circulating total and high-molecular weight (HMW) adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek female population. DESIGN AND METHODS: The two SNPs were genotyped in 349 women without diabetes (mean age: 47.0+/-12.1 years, mean body mass index: 28.9+/-5.6 kg/m(2)). Total and HMW adiponectin concentrations, body composition variables, IR parameters, and plasma lipid levels were determined.
RESULTS: In single SNP analysis adjusting for several potential confounders, SNP +276G>T was associated with higher fasting insulin levels (P=0.01) and higher homeostasis model assessment index for IR (HOMA-IR; P=0.009), and SNP +45T>G was associated with lower insulin levels and HOMA-IR (P=0.05 and P=0.07 respectively). No association with total or HMW adiponectin, plasma lipid levels, and body composition variables was observed; however, haplotype analysis revealed that subjects homozygous for the most common +45T/+276G haplotype had lower total adiponectin levels than did noncarriers of this haplotype (P=0.02). The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage (>or= the population median of 41%; all P<or=0.005), but not among leaner individuals (P for interactions 0.01-0.07), thus suggesting that ADIPOQ effects on insulin sensitivity may depend upon BF status.
CONCLUSION: Our data suggest a significant role of ADIPOQ variants at positions +45 and +276 in the development of IR in healthy Greek women possibly through an interaction with BF.