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World J Gastroenterol. Jun 21, 2014; 20(23): 7347-7355
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7347
Pediatric fatty liver disease: Role of ethnicity and genetics
Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Nicola Santoro
Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Department of Women and Children and General and Specialized Surgery, Seconda Università degli Studi di Napoli, 80138 Naples, Italy
Nicola Santoro, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, United States
Author contributions: The authors conceived and wrote the manuscript.
Supported by The American Heart Association (13SDG14640038) and 2012 Yale Center for Clinical Investigation cholar award to Santoro N; This publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Advancing Translational Science, a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research, Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH
Correspondence to: Nicola Santoro, MD, PhD, Department of Pediatrics, Yale University School of Medicine, 330 Cedar Street, PO Box 208064, New Haven, CT 06520, United States. nicola.santoro@yale.edu
Telephone: +1-203-7376356 Fax: +1-203-7856421
Received: October 8, 2013
Revised: January 4, 2014
Accepted: January 20, 2014
Published online: June 21, 2014
Abstract

Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.

Keywords: Non alcoholic fatty liver disease, Ethnicity, Patatin like phospholipase containing domain 3 gene, Obesity, Insulin resistance, Glucokinase regulatory protein, Apolipoprotein C3 gene, Farnesyl-diphosphate farnesyltransferase 1

Core tip: The prevalence of hepatic steatosis varies among different ethnic groups. Ethnicity with the greatest prevalence of non-alcoholic fatty liver disease (NAFLD) is the Hispanic one followed by Caucasian and then African-Americans. NAFLD exhibits tight links with insulin resistance and metabolic syndrome. Several gene variants have been so far identified by Genome Wide Association Studies or by a candidate gene approach as associated with fatty liver disease. The PNPLA3 rs738409 and the GCKR rs1260326 are the strongest variants associated with fatty liver in paediatrics.