Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study

Peroxisome proliferator-activated receptor gamma (PPAR gamma) and peroxisome proliferator-activated receptor delta (PPAR delta) are promising candidate genes for obesity. Associations between adiposity-related phenotypes and genetic variation in PPAR gamma (Pro12Ala and C1431T), as well as PPAR delta (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 delta T+294C polymorphism or the interaction of the PPAR delta and PPAR gamma variants on adiposity-related phenotypes were observed in any age group or gender. Haplotype-based analysis including both PPAR gamma 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 gamma Pro12Ala and C1431T polymorphisms are associated with increased adiposity during early childhood in a gender- and age-specific manner and independently of the PPAR delta T+294C polymorphism.