OBJECTIVE - The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcnptional activity and plasma IL-6 levels in humans. We addressed the question of whether the C-174G IL-6 polymorphism contributes to variation of insulin sensitivity. RESEARCH DESIGN AND METHODS - Two cohorts of subjects were genotyped. Cohort 1 includes 275 nondiabetic subjects who underwent a euglycemic-hyperinsulinemic clamp. Cohort 2 includes 77 patients with morbid obesity who underwent laparoscopic adjustable gastric banding (LAGB). RESULTS - The genotypes were consistent with Hardy-Weinberg equilibrium proportions. In cohort 1, insulin sensitivity was reduced in carriers of the -174G/G genotype as compared with subjects carrying the C allele (P = 0.004). Carriers of -174G/G displayed significantly higher plasma IL-6 levels in comparison with carriers of the C allele. In a stepwise linear regression analysis, the C-174G polymorphism was independently associated with insulin sensitivity; however, after inclusion of plasma IL-6 concentrations, the polymorphism was excluded from the model explaining insulin sensitivity variability, thus suggesting that the polymorphism was affecting insulin sensitivity by regulating IL-6 plasma levels. IL-6 mRNA levels were measured by real-time RT-PCR in subcutaneous fat obtained from obese patients of cohort 2 during LAGB. Carriers of -174G/G showed increased IL-6 expression compared with subjects carrying the C allele (P = 0.04). There was a significant correlation between adipose IL-6 mRNA expression and insulin resistance assessed by homeostasis model assessment (p = 0.28, P = 0.014). CONCLUSIONS - These results indicate that the -174G/G genotype of the IL-6 gene may contribute to variations in insulin sensitivity. (copyright) 2005 by the American Diabetes Association.
|Titolo:||C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance|
FOLLI, FRANCO (Ultimo)
|Parole Chiave:||adipose tissue; adult; article; cohort analysis; cytokine release; family history; female; fibrinogen blood level; gastric banding; gene expression; genetic linkage; genetic polymorphism; genotype; glucose blood level; glucose clamp technique; heterozygote; human; insulin blood level; insulin resistance; insulin sensitivity; leukocyte count; lipid blood level; major clinical study; male; morbid obesity; promoter region; reverse transcription polymerase chain reaction; statistical analysis; cholesterol; fibrinogen; glucose; high density lipoprotein cholesterol; insulin; interleukin 6; triacylglycerol|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.2337/diacare.28.8.2007|
|Appare nelle tipologie:||01 - Articolo su periodico|