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 (>= the population median of 41%, all P <= 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.