Two polymorphisms in the peroxisome proliferator-activated receptor-γ 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 gamma gene may affect the function of the PPAR gamma and, therefore, body adipocity. 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 gene and their effects on body weight, body composition, and energy expenditure in obese Finns. One hundred and seventy obese subjects [29 men and 141 women; 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 both Ala(12)Ala and CAT478CAT genotypes (n = 5) were significantly more obese 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 conclusion, the Pro(12)Ala and CAC478CAT polymorphisms in the PPAR gamma gene are associated with severe overweight and increased fat mass among obese women.