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IL6 Gene Promoter Polymorphisms and Type 2 Diabetes

Joint Analysis of Individual Participants’ Data From 21 Studies

  1. Cornelia Huth12,
  2. Iris M. Heid1,
  3. Caren Vollmert1,
  4. Christian Gieger12,
  5. Harald Grallert1,
  6. Johanna K. Wolford3,
  7. Birgit Langer1,
  8. Barbara Thorand1,
  9. Norman Klopp1,
  10. Yasmin H. Hamid4,
  11. Oluf Pedersen4,
  12. Torben Hansen4,
  13. Valeriya Lyssenko5,
  14. Leif Groop5,
  15. Christa Meisinger1,
  16. Angela Döring1,
  17. Hannelore Löwel1,
  18. Wolfgang Lieb6,
  19. Christian Hengstenberg7,
  20. Wolfgang Rathmann8,
  21. Stephan Martin8,
  22. Jeffrey W. Stephens9,
  23. Helen Ireland10,
  24. Hugh Mather11,
  25. George J. Miller12,
  26. Heather M. Stringham13,
  27. Michael Boehnke13,
  28. Jaakko Tuomilehto141516,
  29. Heiner Boeing17,
  30. Matthias Möhlig18,
  31. Joachim Spranger18,
  32. Andreas Pfeiffer18,
  33. Ingrid Wernstedt19,
  34. Anders Niklason20,
  35. Abel López-Bermejo21,
  36. José-Manuel Fernández-Real21,
  37. Robert L. Hanson22,
  38. Luis Gallart23,
  39. Joan Vendrell23,
  40. Anastasia Tsiavou24,
  41. Erifili Hatziagelaki25,
  42. Steve E. Humphries10,
  43. H.-Erich Wichmann12,
  44. Christian Herder8 and
  45. Thomas Illig1
  1. 1GSF-Institute of Epidemiology, Neuherberg, Germany
  2. 2Institute of Biometry and Epidemiology, University of Munich, Munich, Germany
  3. 3Translational Genomics Research Institute, Phoenix, Arizona
  4. 4Steno Diabetes Center, Copenhagen, Denmark
  5. 5Department of Clinical Sciences, University Hospital Malmö, Malmö, Sweden
  6. 6Clinic and Policlinic for Internal Medicine II and Institute of Human Genetics, University of Lübeck, Lübeck, Germany
  7. 7Clinic and Policlinic for Internal Medicine II, University of Regensburg, Regensburg, Germany
  8. 8German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  9. 9Medical School, University of Wales, Swansea, U.K
  10. 10Centre for Cardiovascular Genetics, Royal Free and University College Medical School, London, U.K
  11. 11Ealing Hospital, London, U.K
  12. 12Medical Research Council Cardiovascular Research Group, Wolfson Institute of Preventive Medicine, London, U.K
  13. 13Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
  14. 14Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
  15. 15Department of Public Health, University of Helsinki, Helsinki, Finland
  16. 16South Ostrobothnia Central Hospital, Seinäjoki, Finland
  17. 17Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
  18. 18Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany
  19. 19Institute of Neuroscience and Physiology, Sahlgrenska Academy at Gothenborg University, Gothenborg, Sweden
  20. 20Department of Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden
  21. 21Diabetes, Endocrinology and Nutrition Unit, University Hospital Josep Trueta, Girona, Spain
  22. 22National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
  23. 23Research Unit, University Hospital Joan XXIII, Tarragona, Spain
  24. 24Onassis Cardiac Surgery Center, Molecular Immunopathology and Histocompatibility Laboratory, Athens, Greece
  25. 252nd Department of Internal Medicine, University Hospital Attikon, Athens, Greece
  1. Address correspondence and reprint requests to Dr. Thomas Illig, Institute of Epidemiology, GSF-National Research Center for Environment and Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany. E-mail: illig{at}gsf.de

Abstract

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, −174G>C (rs1800795) and −573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 −174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 −573G>C and type 2 diabetes. The observed association of the IL6 −174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted July 12, 2006.
    • Received May 3, 2006.
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This Article

  1. doi: 10.2337/db06-0600 Diabetes October 2006 vol. 55 no. 10 2915-2921
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