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