The Pro12Ala polymorphism of the PPARγ2 gene regulates weight from birth to adulthood

Objective: The Pro12Ala polymorphism in exon B of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene has been related to obesity, insulin resistance, and risk of type 2 diabetes. In this study, the effect of the Pro12Ala polymorphism on long-term changes in weight and body composition was investigated. Research Methods and Procedures: The Pro12Ala polymorphism was genotyped in 311 subjects who participated in our previous population-based study. In that study, weight at birth, 7 years, 20 years, and 41 years, and ponderal index at birth and BMI and waist circumference at 41 years were recorded. Results: The Ala12 allele of the PPARgamma2 gene was associated with high ponderal index at birth (2.77 +/- 0.27 kg/m(3) in subjects with the Ala12Ala genotype, 2.79 +/- 0.29 kg/m(3) in subjects with the Pro12Ala genotype, and 2.63 +/- 0.25 kg/m(3) in subjects with the Pro12Pro genotype, p = 0.007, adjusted for gender) and weight at 7 years (p = 0.045) and tended to be associated with high birth weight (p = 0.094). Subjects with this allele gained less weight between 7 and 20 years (p = 0.043) and more weight between 20 and 41 years (p = 0.001) and ended up having higher waist circumference (p = 0.040) in adulthood than did subjects with the Pro12Pro genotype. Discussion: We conclude that the Pro12Ala polymorphism of the PPARgamma2 gene regulates weight and body composition from utero to adulthood.