The Association of PNPLA3 Variants with Liver Enzymes in Childhood Obesity is Driven by the Interaction with Abdominal Fat

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Dec 6

PMID 22140488

Citations 40

Authors

Emanuele Miraglia Del Giudice

Anna Grandone

Grazia Cirillo

Nicola Santoro

Alessandra Amato

Carmine Brienza

Piera Savarese

Pierluigi Marzuillo

Laura Perrone

Affiliations

Soon will be listed here.

Abstract

Background And Aims: 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.

Methods: 1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.

Results: 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.

Conclusions: 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.

Citing Articles

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