Promoter Polymorphisms of the TNF-α (G-308A) and IL-6 (C-174G) Genes Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

The Finnish Diabetes Prevention Study

  1. Agata Kubaszek1,
  2. Jussi Pihlajamäki1,
  3. Vladislav Komarovski1,
  4. Virpi Lindi2,
  5. Jaana Lindström3,
  6. Johan Eriksson3,
  7. Timo T. Valle3,
  8. Helena Hämäläinen4,
  9. Pirjo Ilanne-Parikka5,
  10. Sirkka Keinänen-Kiukaanniemi6,
  11. Jaakko Tuomilehto37,
  12. Matti Uusitupa2 and
  13. Markku Laakso1
  1. 1Department of Medicine, University of Kuopio, Kuopio, Finland
  2. 2Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
  3. 3Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
  4. 4Research and Development Centre, Social Insurance Institution, Turku, Finland
  5. 5Department of Medicine, Finnish Diabetes Association and University of Tampere, Tampere, Finland
  6. 6Department of Public Health Science and General Practice, University of Oulu, Oulu University Hospital and Department of Sport Medicine, Oulu Deaconess Institute, Oulu, Finland
  7. 7Department of Public Health, University of Helsinki, Helsinki, Finland
  1. Address correspondence and reprint requests to Markku Laakso, Professor and Chair, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi

Abstract

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-α (TNF-α; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The −308A allele of the TNF-α gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05–3.09; P = 0.034). Subjects with both the A allele of the TNF-α gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02–4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the −308A allele of the promoter polymorphism (G-308A) of the TNF-α gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.

Footnotes

    • Accepted April 8, 2003.
    • Received February 9, 2003.
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