The PPARG Pro12Ala Polymorphism Is Associated With a Decreased Risk of Developing Hyperglycemia Over 6 Years and Combines With the Effect of the APM1 G-11391A Single Nucleotide Polymorphism

The Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Study

  1. Riphed Jaziri12,
  2. Stephane Lobbens3,
  3. Roberte Aubert1,
  4. Franck Péan1,
  5. Saida Lahmidi3,
  6. Martine Vaxillaire3,
  7. Isabelle Porchay1,
  8. Naïma Bellili1,
  9. Jean Tichet4,
  10. Beverley Balkau5,
  11. Philippe Froguel36,
  12. Michel Marre127,
  13. Frédéric Fumeron12 and
  14. for the DESIR Study Group*
  1. 1Institut National de la Santé et de la Recherche Médicale (INSERM) U695, Déterminants Génétiques du Diabète de Type 2 et de ses Complications Cardiovasculaires, Faculté Xavier Bichat, Paris, France
  2. 2Université Paris 7 Denis Diderot, Paris, France
  3. 3Centre National de Recherche (CNRS), Unité Mixte de Recherche (UMR) 8090, Institut de Biologie de Lille, Institut Pasteur, Lille, France
  4. 4Institut Régional Pour la Santé, Tours, France
  5. 5INSERM, U258-IFR69, Villejuif, France
  6. 6Imperial College Genome Centre and Genomic Medicine, Imperial College, London, U.K
  7. 7Service d’Endocrinologie, Diabétologie, Nutrition, Groupe Hospitalier Bichat Claude Bernard, Assistance Public-Hôpitaux de Paris (AP-HP), Paris, France
  1. Address correspondence and reprint requests to Frédéric Fumeron, INSERM, U695, Xavier Bichat Medical School, BP 416, 16 rue Henri Huchard, 75870 Paris Cedex 18, France. E-mail: fumeron{at}bichat.inserm.fr

Abstract

Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44–0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44–0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D′ = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.

Footnotes

  • St.L. and R.A. contributed equally to this study.

  • *

    * A complete list of DESIR Study Group members can be found in the appendix.

    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 January 3, 2006.
    • Received May 26, 2005.
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  1. doi: 10.2337/diabetes.55.04.06.db05-0676 Diabetes April 2006 vol. 55 no. 4 1157-1162
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