Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation. Variations in the PPAR g amma gene may affect the function of the PPAR gamma and, therefore, body ad ipocity. We investigated the frequencies of the Pro(12)Ala polymorphism in exon B and the silent CAC478CAT polymorphism in exon 6 of the PPAR gamma ge ne and their effects on body weight, body composition, and energy expenditu re in obese Finns. One hundred and seventy obese subjects [29 men and 141 w omen; body mass index (BMI), 35.7 +/- 3.8 kg/m(2); age, 43 +/- 8 yr; mean /- SD] participated in the study. The frequencies of the Ala(12) allele in exon B and CAT478 allele in exon 6 were not significantly different between the obese and population-based control subjects (0.14 vs. 0.13 and 0.19 us . 0.21, respectively). The polymorphisms were associated with increased BMI [Pro(12)Pro, 34.5 +/- 3.8; Pro(12)Ala, 34.8 +/- 3.1; Ala(12)Ala, 39.2 +/- 4.6 kg/m(2) (P = 0.011); CAC478CAC, 34.5 +/- 3.8; CAC478CAT, 34.5 +/- 3.3; CAT478CAT, 37.7 +/- 4.1 kg/m(2) (P = 0.046)]. In addition, the women with b oth Ala(12)Ala and CAT478CAT genotypes (n = 5) were significantly more obes e compared with the women having both Pro(12)Pro and CAC478CAC genotypes (n = 85; BMI, 40.6 +/- 3.3 vs. 34.4 +/- 3.9 kg/m(2); P = 0.001), and they had increased fat mass (46.8 +/- 9.1 us. 36.8 +/- 7.5 kg; P = 0.005). In concl usion, the Pro(12)Ala and CAC478CAT polymorphisms in the PPAR gamma gene ar e associated with severe overweight and increased fat mass among obese wome n.