The Effects of the Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor-γ2 Gene on Insulin Sensitivity and Insulin Metabolism Interact With Size at Birth

  1. Johan G. Eriksson1,
  2. Virpi Lindi2,
  3. Matti Uusitupa2,
  4. Tom J. Forsén3,
  5. Markku Laakso4,
  6. Clive Osmond5 and
  7. David J.P. Barker5
  1. 1Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
  2. 2Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio, Finland
  3. 3Department of Public Health, University of Helsinki, Helsinki, Finland
  4. 4Department of Medicine, University of Kuopio, Kuopio, Finland
  5. 5MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, U.K.

    Abstract

    Type 2 diabetes is known to be associated with a small body size at birth. Body size at birth is an indicator of the intrauterine environment. There is also a well-established association between the peroxisome proliferator-activated receptor (PPAR)-γ2 gene and type 2 diabetes. We therefore assessed whether the effects of the Pro12Ala polymorphism of the PPAR-γ2 gene on insulin sensitivity and insulin concentrations in adult life are modified by size at birth. We found that the effects of the Pro12Pro and Pro12Ala polymorphisms of the PPAR-γ2 gene in elderly people depended on their body size at birth. The well-known association between small body size at birth and insulin resistance was seen only in individuals with the high-risk Pro12Pro allele. In those who had low birth weight, the Pro12Pro polymorphism of the PPAR-γ2 gene was associated with increased insulin resistance (P < 0.002) and elevated insulin concentrations (P < 0.003). These interactions between the effects of the Pro12Ala polymorphisms of the PPAR-γ2 gene on adult traits and the effects of birth weight link two previously unknown associations together within the context of type 2 diabetes. We suggest that these findings reflect gene-environment interaction.

    Footnotes

    • Address correspondence and reprint requests to Dr. Johan Eriksson, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, FIN-00300 Helsinki, Finland. E-mail: johan.eriksson{at}ktl.fi.

      Received for publication 16 February 2002 and accepted in revised form 3 April 2002.

      HOMA-IR, homeostasis model assessment for insulin resistance; PPAR, peroxisome proliferator-activated receptor.

    | Table of Contents