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.
Yang
Xiaolin
X
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Jansson
Per-Anders
PA
Pellmé
Fredrik
F
Laakso
Markku
M
Smith
Ulf
U
D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism; D000483:Alleles; D005215:Fasting; D015870:Gene Expression; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D052242:Adiponectin; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D012333:RNA, Messenger