RT Journal Article
SR Electronic
T1 C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 2007
OP 2012
DO 10.2337/diacare.28.8.2007
VO 28
IS 8
A1 Cardellini, Marina
A1 Perego, Lucia
A1 D’Adamo, Monica
A1 Marini, Maria Adelaide
A1 Procopio, Cristina
A1 Hribal, Marta Letizia
A1 Andreozzi, Francesco
A1 Frontoni, Simona
A1 Giacomelli, Maurizio
A1 Paganelli, Michele
A1 Pontiroli, Antonio E.
A1 Lauro, Renato
A1 Folli, Franco
A1 Sesti, Giorgio
YR 2005
UL http://care.diabetesjournals.org/content/28/8/2007.abstract
AB OBJECTIVE—The C-174G promoter polymorphism of the interleukin (IL)-6 gene was found to influence transcriptional 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 (ρ = 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.