C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance.
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.


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 (rho = 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.
Cardellini
Marina
M
Department of Internal Medicine, University of Rome, Italy.
Perego
Lucia
L
D'Adamo
Monica
M
Marini
Maria Adelaide
MA
Procopio
Cristina
C
Hribal
Marta Letizia
ML
Andreozzi
Francesco
F
Frontoni
Simona
S
Giacomelli
Maurizio
M
Paganelli
Michele
M
Pontiroli
Antonio E
AE
Lauro
Renato
R
Folli
Franco
F
Sesti
Giorgio
G
D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D015331:Cohort Studies; D005260:Female; D015390:Gastric Bypass; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D009767:Obesity, Morbid / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values
D015850:Interleukin-6