Effect of the interleukin-6 (-174) g/c promoter polymorphism on adiponectin and insulin sensitivity.

We investigated the relation among the interleukin (IL)-6 (-174) G/C promoter polymorphism, adipose tissue gene expression of IL6, circulating adiponectin, and systemic insulin sensitivity. Eighty-five Swedish male subjects who had participated in our previous prediabetic phenotype characterization study were genotyped for the IL6 (-174) G/C polymorphism. Subcutaneous adipose tissue gene expression of IL6 and adiponectin was measured in 44 subjects. The IL6 (-174) G allele carriers had higher fasting plasma insulin levels (C/C, 7.8 +/- 1.1; G/C, 9.0 +/- 0.6; G/G, 10.5 +/- 1.0 mU/L) and higher homeostasis model assessment for insulin resistance (C/C, 1.6 +/- 0.2; G/C, 1.9 +/- 0.1; G/G, 2.2 +/- 0.2) compared with subjects with the C/C genotype. The circulating adiponectin levels were lower in the G allele carriers (C/C, 7.93 +/- 0.45; G/C, 7.05 +/- 0.44; G/G, 7.02 +/- 0.46 microg/mL), whereas the IL-6 levels did not differ among the three genotypes. Adipose tissue IL6 gene expression was significantly higher in the G allele carriers compared with the subjects homozygous for the C allele (C/C, 0.29 +/- 0.15; G/C, 0.84 +/- 0.29; G/G, 0.62 +/- 0.35). Our results suggest that IL6 (-174) G/C polymorphism is associated with insulin resistance and increased adipose tissue IL6 gene expression, which can impair adiponectin production.