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

Faculty of Biomedical and Life Sciences, Institute of Diet, Exercise and Lifestyle (IDEAL), University of Glasgow, Glasgow, UK.
Obesity (Impact Factor: 3.73). 05/2008; 16(4):913-8. DOI: 10.1038/oby.2008.1
Source: PubMed


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.

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Available from: George Moschonis, Jul 28, 2014
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    • "The widely studied P12A polymorphism of PPARG has been shown to be associated with various metabolic disorders, including obesity and type 2 diabetes in adults. The attempts to assess the role of P12A on the susceptibility to obesity in children have provided inconsistent reports (19,20). Our study did not detect any association of PPARG variants with childhood obesity. "
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    ABSTRACT: The increasing prevalence of obesity in urban Indian children is indicative of an impending crisis of metabolic disorders. Although perturbations in the secretion of adipokines and inflammatory molecules in childhood obesity are well documented, the contribution of common variants of genes encoding them is not well investigated. We assessed the association of 125 common variants from 21 genes, encoding adipocytokines and inflammatory markers in 1,325 urban Indian children (862 normal weight [NW group] and 463 overweight/obese [OW/OB group]) and replicated top loci in 1,843 Indian children (1,399 NW children and 444 OW/OB children). Variants of four genes (PBEF1 [rs3801266] [P = 4.5 × 10(-4)], IL6 [rs2069845] [P = 8.7 × 10(-4)], LEPR [rs1137100] [P = 1.8 × 10(-3)], and IL6R [rs7514452] [P = 2.1 × 10(-3)]) were top signals in the discovery sample. Associations of rs2069845, rs1137100, and rs3801266 were replicated (P = 7.9 × 10(-4), 8.3 × 10(-3), and 0.036, respectively) and corroborated in meta-analysis (P = 2.3 × 10(-6), 3.9 × 10(-5), and 4.3 × 10(-4), respectively) that remained significant after multiple testing corrections. These variants also were associated with quantitative measures of adiposity (weight, BMI, and waist and hip circumferences). Allele dosage analysis of rs2069845, rs1137100, and rs3801266 revealed that children with five to six risk alleles had an approximately four times increased risk of obesity than children with less than two risk alleles (P = 1.2 × 10(-7)). In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children.
    Diabetes 03/2012; 61(3):626-31. DOI:10.2337/db11-1501 · 8.10 Impact Factor
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    • "PPARγ2 Pro12Ala mutation has been also shown to enhance weight loss brought about by exercise in offspring of type 2 diabetic subject [61] or prevent body weight regain after weight loss [62–64]. However, numerous studies suggests an association of Ala12 variant with increased risk of obesity, including studies in ethnic populations of Mexican Americans [65], male Spanish adults [66] or Spanish children and adolescents [67], French [68], male white Italians [69], French Canadians [70], male Brazilians of European descent [71], native Javanese [72], Uygurs, Kazaks, Hans (Chinese) [73], and Greek young girls [74]. This association can also be found in nondiabetic and nonobese or obese Americans [75], obese Finnish women [76], overweight Korean female subjects [but not in lean female subjects] [77] and in Turkish women with gestational diabetes [78]. "
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    ABSTRACT: The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.
    PPAR Research 02/2009; 2009:849538. DOI:10.1155/2009/849538 · 1.64 Impact Factor
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    • "The activation of PPARD results in the increased expression of genes involved in lipid uptake, fatty acid oxidation and uncoupling proteins, highlighting the PPARD prominent role in mitochondrial activity [13,14]. PPARD gene variants have been associated with obesity [15-17], although some authors have failed to replicate this finding [18-21]. Recent reports have associated PPARD polymorphisms with the effectiveness of cardiovascular fitness, demonstrating the pivotal role of PPARD gene variants in mitochondrial function and, in consequence, in weight control [22,23]. "
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    ABSTRACT: Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Cross-sectional, genetic association study and gene-gene interaction analysis. The study sample comprise 1953 individuals, 725 obese (defined as body mass index > or = 30) and 1228 non obese subjects. In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04-1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Our results suggest that CAPN5 and PPARD gene products may also interact in vivo.
    Cardiovascular Diabetology 07/2008; 7(1):23. DOI:10.1186/1475-2840-7-23 · 4.02 Impact Factor
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