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; C45TOG, rs2241766 and C276GOT, 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: 47.0G12.1 years, mean body mass index: 28.9G5.6 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 C276GO Tw as associated with higher fasting insulin levels (PZ0.01) and higher homeostasis model assessment index for IR (HOMA-IR; PZ0.009), and SNP C45TOG was associated with lower insulin levels and HOMA-IR (PZ0.05 and PZ0.07 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 C45T/C276G haplotype had lower total adiponectin levels than did noncarriers of this haplotype (PZ0.02). The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage (R 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 C45 and C276 in the development of IR in healthy Greek women possibly through an interaction with BF.