The effects of the Pro12Ala polymorphism of the PPARgamma-2 gene on lipid metabolism interact with body size at birth.

Body size at birth is an indicator of the intrauterine environment. The effects of the Pro12Pro genotype and the 12Ala allele of the PPARgamma-2 gene on glucose and insulin metabolism in adult life depend on body size at birth. A low birth weight is associated with insulin resistance and type 2 diabetes. The peroxisome proliferator-activated receptor-gamma (PPARgammas) are also regulators of adipocyte differentiation, and the PPARgamma-2 gene could also contribute to the development of dyslipidemia. Therefore, the effects of the Pro12Ala polymorphisms of the PPARgamma-2 gene on lipid metabolism were measured in 476 elderly persons whose birth weight was known. The Ala12 allele was associated with increased serum total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol concentrations but only among those who had birth weights below 3000 g. These interactions between the effects of the PPARgamma-2 gene on adult traits and the effects of birth weight may be interpreted as examples of gene-environmental interactions, which underlie plasticity during development.