title: The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity.
abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in many tissues. IL-6 null mice show low energy expenditure, but the effect of the variants of the IL-6 gene on energy expenditure has not been previously studied in humans. Therefore, we investigated the effect of the C-174G promoter polymorphism of the IL-6 gene on energy expenditure, measured by indirect calorimetry in healthy Finnish subjects (n = 124). We also measured insulin sensitivity by the hyperinsulinemic-euglycemic clamp. Subjects with the C-174C genotype of the IL-6 gene had significantly lower energy expenditure than subjects with the G-174C or G-174G genotypes both in fasting (CC 13.68 +/- 1.98, CG 14.73 +/- 1.57, GG 14.81 +/- 2.01 kcal x kg(-1) x min(-1); P = 0.012) and during the euglycemic-hyperinsulinemic clamp (CC 15.24 +/- 2.05, CG 16.62 +/- 2.06, GG 16.66 +/- 2.50 kcal x kg(-1) x min(-1); P = 0.007). Moreover, subjects homozygous for the C allele had lower rates of whole-body glucose uptake than carriers of the G allele (CC 50.95 +/- 13.91, CG 59.40 +/- 14.17, GG 59.21 +/- 15.93 micro mol x kg(-1) x min(-1); P = 0.016). The rates of both oxidative (P = 0.013) and nonoxidative (P = 0.016) glucose disposal were significantly affected by the IL-6 promoter polymorphism. In conclusion, the C-174C promoter polymorphism of the IL-6 gene influences energy expenditure and insulin sensitivity in healthy normoglycemic subjects. Whether this polymorphism is a risk factor for obesity or type 2 diabetes can be estimated only in prospective population-based studies.
authors.affiliation: Department of Medicine, University of Kuopio, Finland.
authors.forename: Agata
authors.initials: A
authors.lastname: Kubaszek
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Kari
authors.initials: K
authors.lastname: Punnonen
authors.forename: Pauli
authors.initials: P
authors.lastname: Karhapää
authors.forename: Ilkka
authors.initials: I
authors.lastname: Vauhkonen
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002151:Calorimetry; D004734:Energy Metabolism / Q000235:genetics*; D005215:Fasting; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D005947:Glucose