PPAR-γ2 Pro12Ala Variant Is Associated with Greater Insulin Sensitivity in Childhood Obesity

Buzzetti, Raffaella; Petrone, Antonio; Caiazzo, Assunta M; Alemanno, Irene; Zavarella, Sara; Capizzi, Marco; Mein, Charles A.; Osborn, John; Vania, Andrea; Mario, U. Di

doi:10.1203/01.pdr.0000147728.62185.21

Cited by 39 publications

(30 citation statements)

References 18 publications

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“…Research into variation at the PPARG locus and BMI has largely involved adults, but in a follow up study on weight and body composition, Pro12Ala was shown to regulate weight and body composition from birth through to adulthood (Pihlajamaki et al, 2004). Importantly, the alanine substitution has been associated with reduced BMI and increased insulin sensitivity in children (Buzzetti et al, 2005;Cecil et al, 2005;Dedoussis et al, 2009), indicating that this variant confers some sort of protection from obesity and type 2 diabetes at an early age. These data support much of the evidence in adults (Deeb et al, 1998;Doney et al, 2004), though reports are inconsistent (Hamann et al, 1999;Lagou et al, 2008;Scaglioni et al, 2006), possibly because of the action of multiple variants within the PPARG gene itself (Doney et al, 2004), and or other gene-gene and gene-environment interactions.…”

Section: Peroxisome Proliferator-activated Receptor Gene -A Candidatementioning

confidence: 99%

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent ' obesogenic ' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coeffi cients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated ( FTO ), peroxisome proliferator-activated receptor ( PPARG ) and melanocortin 4 receptor ( MC4R ) which contribute to variance in BMI also infl uence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specifi c allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.

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Section: Peroxisome Proliferator-activated Receptor Gene -A Candidatementioning

confidence: 99%

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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“…Buzzetti et al (2005) and Tavares et al (2005) have shown that PPARg activation significantly increases insulin sensitivity, ameliorates high blood pressure and dyslipidemia, improves large blood vessel and microvascular lesions in patients with type 2 diabetes, and reduces the risk of cardiovascular disease. Regarding the relationship between the PPARg2 gene Pro12Ala variants and hypertension, some domestic and international research has drawn different conclusions, especially when different geographic regions and ethnicities are involved.…”

Section: Introductionmentioning

confidence: 99%

Association of the PPARγ2 gene Pro12Ala variant with primary hypertension and metabolic lipid disorders in Han Chinese of Inner Mongolia

Gao¹,

Wang²,

Yun³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. In order to determine whether Pro12Ala polymorphism of the peroxisome proliferator-activated receptor g2 (PPARg2) gene contributes to susceptibility to primary hypertension and metabolic lipid disorders, 482 unrelated subjects from Inner Mongolia were studied, including 137 healthy normotensive (controls) and 345 hypertensive subjects. PCR-RFLP was used to determine the genotypes of Pro12Ala variants of the PPARg2 gene, and direct sequencing was used to check the results. The frequency of the Ala allele was lower in patients with hypertension (1.3%) than in controls (3.6%). The incidence of the Ala allele was significantly lower in patients with hypertension (P = 0.018) 1313©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 9 (3): 1312-1320 (2010) PPARg2 and primary hypertension in Han Chinese and in those with elevated blood lipids (P = 0.040), compared to the control group. Total plasma cholesterol, triglycerides and high-density lipoprotein cholesterol were significantly higher (P < 0.05), and lowdensity lipoprotein cholesterol was significantly lower (P < 0.05) in primary hypertension patients than in the control group. We conclude that the Ala allele is involved in genetic susceptibility to hypertension and metabolic lipid disorders in the Han population of Inner Mongolia.

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“…In a smaller subgroup with DEXA scans, we found no support for this hypothesis. In SGA children who caught up to a normal height and subjects with type 2 DM or obesity (4,(22)(23)(24)(25)(26), results about the association between Pro12Ala and estimates of glucose homeostasis and blood pressure have been conflicting. A population of short SGA children had not been studied yet.…”

Section: Discussionmentioning

confidence: 99%

The PPAR-γ Pro12Ala polymorphism associates with weight gain during GH-treatment in short children born small for gestational age

Kort

Hokken-Koelega²

2010

European Journal of Endocrinology

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Context: Short children born small for gestational age (SGA) have a lean phenotype with lower insulin sensitivity and higher blood pressure. GH treatment results in weight gain, and a decrease in blood pressure and insulin sensitivity. However, not all children respond in the same way. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR-g) gene is inversely associated with body mass index (BMI), changes in BMI and the risk to develop type 2 diabetes mellitus. Objective: To analyze the contribution of the PPAR-g Pro12Ala polymorphism to GH induced changes in determinants of metabolic and cardiovascular disease in short SGA children. Methods: PPAR-g was genotyped in 238 Caucasian short SGA children (mean age 7.5 years). Height, weight, blood pressure, and serum lipids were measured before start and during 4 years of GH treatment. In addition, glucose homeostasis by homeostasis model assessment insulin resistance ratio (HOMA-IR) (nZ148) and by frequently sampled i.v. glucose tolerance test (nZ51), and body composition by dual energy X-ray absorptiometry (nZ79) were measured. Results: At baseline, the Ala12 allele was not associated with any determinant of metabolic and cardiovascular disease. After 4 years of GH treatment, the increase in weight for height SDS and BMI SDS was significantly greater in carriers of an Ala12 allele than in noncarriers. The change in all other parameters was not associated with Pro12Ala genotype. Conclusion: The Ala12 variant of the PPAR-g gene is associated with higher weight gain during GH treatment but not with changes in determinants of metabolic and cardiovascular diseases in Caucasian subjects born SGA.

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PPAR-γ2 Pro12Ala Variant Is Associated with Greater Insulin Sensitivity in Childhood Obesity

Cited by 39 publications

References 18 publications

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Association of the PPARγ2 gene Pro12Ala variant with primary hypertension and metabolic lipid disorders in Han Chinese of Inner Mongolia

The PPAR-γ Pro12Ala polymorphism associates with weight gain during GH-treatment in short children born small for gestational age

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