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

• DOI: 10.2337/diabetes.51.7.2321
• Publication Date: 2007-03-06T19:04:22Z
• Authors: Johan G. Eriksson; Virpi Lindi; Matti Uusitupa; Tom J. Forsén; Markku Laakso; Clive Osmond; David J.P. Barker
• Keywords: Male; 0301 basic medicine; Alanine; Proline; Infant, Newborn; 610; Receptors, Cytoplasmic and Nuclear; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Amino Acid Substitution; Diabetes Mellitus, Type 2; Birth Weight; Humans; Insulin; Female; Transcription Factors

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.