Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2007-2012 |
| Number of pages | 6 |
| Journal | Diabetes Care |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance. / Cardellini, Marina; Perego, Lucia; D'Adamo, Monica; Marini, Maria Adelaide; Procopio, Cristina; Hribal, Marta Letizia; Andreozzi, Francesco; Frontoni, Simona; Giacomelli, Maurizio; Paganelli, Michele; Pontiroli, Antonio E.; Lauro, Renato; Folli, Franco; Sesti, Giorgio.
In: Diabetes Care, Vol. 28, No. 8, 08.2005, p. 2007-2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance
AU - Cardellini, Marina
AU - Perego, Lucia
AU - D'Adamo, Monica
AU - Marini, Maria Adelaide
AU - Procopio, Cristina
AU - Hribal, Marta Letizia
AU - Andreozzi, Francesco
AU - Frontoni, Simona
AU - Giacomelli, Maurizio
AU - Paganelli, Michele
AU - Pontiroli, Antonio E.
AU - Lauro, Renato
AU - Folli, Franco
AU - Sesti, Giorgio
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=23044505300&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23044505300&partnerID=8YFLogxK
U2 - 10.2337/diacare.28.8.2007
DO - 10.2337/diacare.28.8.2007
M3 - Article
C2 - 16043746
AN - SCOPUS:23044505300
VL - 28
SP - 2007
EP - 2012
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 8
ER -