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

Marina Cardellini, Lucia Perego, Monica D'Adamo, Maria Adelaide Marini, Cristina Procopio, Marta Letizia Hribal, Francesco Andreozzi, Simona Frontoni, Maurizio Giacomelli, Michele Paganelli, Antonio E. Pontiroli, Renato Lauro, Franco Folli, Giorgio Sesti

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)2007-2012
Number of pages6
JournalDiabetes Care
Volume28
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

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Insulin Resistance
Interleukin-6
Genes
Alleles
Genotype
Stomach
Messenger RNA
Glucose Clamp Technique
Morbid Obesity
Subcutaneous Fat
Real-Time Polymerase Chain Reaction
Linear Models
Homeostasis
Research Design
Regression Analysis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cardellini, M., Perego, L., D'Adamo, M., Marini, M. A., Procopio, C., Hribal, M. L., ... Sesti, G. (2005). C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance. Diabetes Care, 28(8), 2007-2012. https://doi.org/10.2337/diacare.28.8.2007

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 journalArticle

Cardellini, M, Perego, L, D'Adamo, M, Marini, MA, Procopio, C, Hribal, ML, Andreozzi, F, Frontoni, S, Giacomelli, M, Paganelli, M, Pontiroli, AE, Lauro, R, Folli, F & Sesti, G 2005, 'C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance', Diabetes Care, vol. 28, no. 8, pp. 2007-2012. https://doi.org/10.2337/diacare.28.8.2007
Cardellini M, Perego L, D'Adamo M, Marini MA, Procopio C, Hribal ML et al. C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance. Diabetes Care. 2005 Aug;28(8):2007-2012. https://doi.org/10.2337/diacare.28.8.2007
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. / C-174G polymorphism in the promoter of the interleukin-6 gene is associated with insulin resistance. In: Diabetes Care. 2005 ; Vol. 28, No. 8. pp. 2007-2012.
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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

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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.

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