Impact of Peroxisome Proliferator–activated Receptors γ and δ on Adiposity in Toddlers and Preschoolers in the GENESIS Study

Peroxisome proliferator–activated receptor γ ( PPAR γ) and peroxisome proliferator–activated receptor δ ( PPAR δ) are promising candidate genes for obesity. Associations between adiposity‐related phenotypes and genetic variation in PPAR γ (Pro12Ala and C1431T), as well as PPAR δ (T+294C) were assessed in 2,102 Greek children aged 1–6 years, as part of a large‐scale epidemiological study (Growth, Exercise and Nutrition Epidemiological Study In preSchoolers). In girls aged 3–4 years, the Ala12 allele was associated with higher mid‐upper arm ( P = 0.010) and hip ( P = 0.005) circumferences, as well as subscapular ( P = 0.008) and total skinfolds ( P = 0.011) that explained 2.0, 3.7, 2.1, and 1.9% of the phenotypic variance, respectively, while the T1431 allele was associated with higher mean values for waist circumference ( P = 0.018) and suprailiac skinfold ( P = 0.017), genotype accounting for 1.6% of the variance in both phenotypes. No significant effects of PPAR δ T+294C polymorphism or the interaction of the PPAR δ and PPAR γ variants on adiposity‐related phenotypes were observed in any age group or gender. Haplotype‐based analysis including both PPAR γ polymorphisms revealed that in girls aged 3–4 years, the Ala‐T haplotype was associated with higher waist ( P = 0.014) and hip ( P = 0.007) circumferences compared to the common Pro‐C haplotype. The PPAR γ Pro12Ala and C1431T polymorphisms are associated with increased adiposity during early childhood in a gender‐ and age‐specific manner and independently of the PPAR δ T+294C polymorphism.