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Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes

C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance

  1. Marina Cardellini, MD1,
  2. Lucia Perego, PHD2,
  3. Monica D’Adamo, MD1,
  4. Maria Adelaide Marini, MD1,
  5. Cristina Procopio3,
  6. Marta Letizia Hribal, PHD13,
  7. Francesco Andreozzi, MD3,
  8. Simona Frontoni, MD1,
  9. Maurizio Giacomelli, MD4,
  10. Michele Paganelli, MD4,
  11. Antonio E. Pontiroli, MD5,
  12. Renato Lauro, MD1,
  13. Franco Folli, MD2 and
  14. Giorgio Sesti, MD1
  1. 1Department of Internal Medicine, University of Rome, Rome, Italy
  2. 2Divisione di Medicina Interna, San Raffaele Hospital, Milan, Italy
  3. 3Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia di Catanzaro, Catanzaro, Italy
  4. 4Divisione di Chirurgia Generale, San Raffaele Hospital, Milan, Italy
  5. 5Universita di Milano, Cattedra di Medicina Interna, Milan, Italy
  1. Franco Folli, MD, PhD, Department of Internal Medicine, San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy. E-mail: folli.franco{at}hsr.it
  2. Address correspondence and reprint requests to Giorgio Sesti, MD, Dipartimento Medicina Sperimentale e Clinica, Università Magna-Græcia di Catanzaro, Via Campanella 115, 88100 Catanzaro, Italy. E-mail: sesti{at}unicz.it
Diabetes Care 2005 Aug; 28(8): 2007-2012. https://doi.org/10.2337/diacare.28.8.2007
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Abstract

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.

  • IL, interleukin
  • LAGB, laparoscopic adjustable gastric banding

Footnotes

  • M.C., L.P., and M.D. contributed equally to this work.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted May 1, 2005.
    • Received December 16, 2004.
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August 2005, 28(8)
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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
Diabetes Care Aug 2005, 28 (8) 2007-2012; DOI: 10.2337/diacare.28.8.2007

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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
Diabetes Care Aug 2005, 28 (8) 2007-2012; DOI: 10.2337/diacare.28.8.2007
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