The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.

<h4>Background and aims</h4>A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analy...

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Autores principales:	Emanuele Miraglia del Giudice, Anna Grandone, Grazia Cirillo, Nicola Santoro, Alessandra Amato, Carmine Brienza, Piera Savarese, Pierluigi Marzuillo, Laura Perrone
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57375d409ca54adb9abdbe4642d68610
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spelling	oai:doaj.org-article:57375d409ca54adb9abdbe4642d686102021-11-18T07:33:31ZThe association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.1932-620310.1371/journal.pone.0027933https://doaj.org/article/57375d409ca54adb9abdbe4642d686102011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140488/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and aims</h4>A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.<h4>Methods</h4>1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.<h4>Results</h4>Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.<h4>Conclusions</h4>We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.Emanuele Miraglia del GiudiceAnna GrandoneGrazia CirilloNicola SantoroAlessandra AmatoCarmine BrienzaPiera SavaresePierluigi MarzuilloLaura PerronePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27933 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emanuele Miraglia del Giudice Anna Grandone Grazia Cirillo Nicola Santoro Alessandra Amato Carmine Brienza Piera Savarese Pierluigi Marzuillo Laura Perrone The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
description	<h4>Background and aims</h4>A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.<h4>Methods</h4>1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.<h4>Results</h4>Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.<h4>Conclusions</h4>We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.
format	article
author	Emanuele Miraglia del Giudice Anna Grandone Grazia Cirillo Nicola Santoro Alessandra Amato Carmine Brienza Piera Savarese Pierluigi Marzuillo Laura Perrone
author_facet	Emanuele Miraglia del Giudice Anna Grandone Grazia Cirillo Nicola Santoro Alessandra Amato Carmine Brienza Piera Savarese Pierluigi Marzuillo Laura Perrone
author_sort	Emanuele Miraglia del Giudice
title	The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
title_short	The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
title_full	The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
title_fullStr	The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
title_full_unstemmed	The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
title_sort	association of pnpla3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/57375d409ca54adb9abdbe4642d68610
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The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat.

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