Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity

Alessia Di Costanzo; Lucia Pacifico; Claudio Chiesa; Francesco Massimo Perla; Fabrizio Ceci; Antonio Angeloni; Laura D'Erasmo; Michele Di Martino; Marcello Arca

doi:10.1038/s41390-019-0303-1

Genetic and metabolic predictors of hepatic fat content in a cohort of Italian children with obesity

Pediatr Res. 2019 Apr;85(5):671-677. doi: 10.1038/s41390-019-0303-1. Epub 2019 Jan 23.

Authors

Alessia Di Costanzo¹, Lucia Pacifico², Claudio Chiesa³, Francesco Massimo Perla², Fabrizio Ceci⁴, Antonio Angeloni⁴, Laura D'Erasmo⁵, Michele Di Martino⁶, Marcello Arca⁵

Affiliations

¹ Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161, Rome, Italy. alessia.dicostanzo@uniroma1.it.
² Department of Pediatrics, Sapienza University of Rome, 00161, Rome, Italy.
³ Institute of Translational Pharmacology, National Research Council, 00133, Rome, Italy.
⁴ Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy.
⁵ Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, 00161, Rome, Italy.
⁶ Department of Radiology, Sapienza University of Rome, 00161, Rome, Italy.

Abstract

Objectives: To comprehensively explore metabolic and genetic contributors to liver fat accumulation in overweight/obese children.

Methods: Two hundred thirty Italian children with obesity were investigated for metabolic parameters and genotyped for PNPLA3, TM6SF2, GCKR, and MBOAT7 gene variants. Percentage hepatic fat content (HFF%) was measured by nuclear magnetic resonance.

Results: HFF% was positively related with BMI, HOMA_IR, metabolic syndrome, ALT, AST, γGT, and albumin. Carriers of [G] allele in PNPLA3, [T] allele in GCKR and [T] allele in TM6SF2 genes had significantly higher hepatic fat content than wild-type carriers. HFF% was explained for 8.7% by metabolic and for 16.1% by genetic factors and, a model including age, gender, BMI, HOMA_IR, PNPLA3, GCKR, and TM6SF2 variants was the best predictor of HFF%, explaining 24.8% of its variation (P < 0.001). A weighted-genetic risk score combining PNPLA3, GCKR, and TM6SF2 risk alleles was associated with almost eightfold higher risk of NAFLD.

Conclusions: Our data highlighted the predominant role of genetic factors in determining the amount of liver fat content in children with obesity.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Acyltransferases / genetics
Adaptor Proteins, Signal Transducing / genetics
Adipose Tissue / metabolism*
Adolescent
Alleles
Body Mass Index
Child
DNA / analysis
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Italy / epidemiology
Lipase / genetics
Liver / diagnostic imaging
Liver / pathology*
Magnetic Resonance Spectroscopy
Male
Membrane Proteins / genetics
Non-alcoholic Fatty Liver Disease / diagnostic imaging
Non-alcoholic Fatty Liver Disease / genetics*
Overweight
Pediatric Obesity / epidemiology*
Pediatric Obesity / genetics*
Risk

Substances

Adaptor Proteins, Signal Transducing
GCKR protein, human
Membrane Proteins
TM6SF2 protein, human
DNA
Acyltransferases
MBOAT7 protein, human
Lipase
adiponutrin, human