Polymorphisms in the SLC2A2 (GLUT2) Gene Are Associated With the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes

The Finnish Diabetes Prevention Study

  1. Olli Laukkanen1,
  2. Jaana Lindström2,
  3. Johan Eriksson2,
  4. Timo T. Valle2,
  5. Helena Hämäläinen3,
  6. Pirjo Ilanne-Parikka4,
  7. Sirkka Keinänen-Kiukaanniemi56,
  8. Jaakko Tuomilehto27,
  9. Matti Uusitupa8 and
  10. Markku Laakso1
  1. 1Department of Medicine, University of Kuopio, Kuopio, Finland
  2. 2Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
  3. 3Research Department, Social Insurance Institution, Turku, Finland
  4. 4Finnish Diabetes Association and Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
  5. 5Department of Public Health Science and General Practice, University of Oulu, Oulu University Hospital, Oulu, Finland
  6. 6Department of Sport Medicine, Oulu Deaconess Institute, Oulu, Finland
  7. 7Department of Public Health, University of Helsinki, Helsinki, Finland
  8. 8Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
  1. Address correspondence and reprint requests to Prof. Markku Laakso, MD, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi

Abstract

Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1α], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34–6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype carriers was increased in the control group (5.56 [1.78–17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT.

Footnotes

    • Accepted April 18, 2005.
    • Received February 9, 2005.
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