PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain...

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Autores principales:	Claudia Vales-Villamarín, Olaya de Dios, Iris Pérez-Nadador, Teresa Gavela-Pérez, Leandro Soriano-Guillén, Carmen Garcés
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PPARγ2 Pro12Ala polymorphism insulin HOMA obesity body mass index (BMI) children Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0092dff9f643446e9d30078ed4f14d75
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spelling	oai:doaj.org-article:0092dff9f643446e9d30078ed4f14d752021-11-30T12:38:53ZPPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes1663-981210.3389/fphar.2021.763853https://doaj.org/article/0092dff9f643446e9d30078ed4f14d752021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.763853/fullhttps://doaj.org/toc/1663-9812Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.Claudia Vales-VillamarínOlaya de DiosIris Pérez-NadadorTeresa Gavela-PérezLeandro Soriano-GuillénCarmen GarcésFrontiers Media S.A.articlePPARγ2 Pro12Ala polymorphisminsulinHOMAobesitybody mass index (BMI)childrenTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PPARγ2 Pro12Ala polymorphism insulin HOMA obesity body mass index (BMI) children Therapeutics. Pharmacology RM1-950
spellingShingle	PPARγ2 Pro12Ala polymorphism insulin HOMA obesity body mass index (BMI) children Therapeutics. Pharmacology RM1-950 Claudia Vales-Villamarín Olaya de Dios Iris Pérez-Nadador Teresa Gavela-Pérez Leandro Soriano-Guillén Carmen Garcés PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
description	Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPARγ are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPARγ on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPARγ2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPARγ2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPARγ2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.
format	article
author	Claudia Vales-Villamarín Olaya de Dios Iris Pérez-Nadador Teresa Gavela-Pérez Leandro Soriano-Guillén Carmen Garcés
author_facet	Claudia Vales-Villamarín Olaya de Dios Iris Pérez-Nadador Teresa Gavela-Pérez Leandro Soriano-Guillén Carmen Garcés
author_sort	Claudia Vales-Villamarín
title	PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
title_short	PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
title_full	PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
title_fullStr	PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
title_full_unstemmed	PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes
title_sort	pparγ2 pro12ala polymorphism is associated in children with traits related to susceptibility to type 2 diabetes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0092dff9f643446e9d30078ed4f14d75
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PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

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