title: Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study.
abstract: We assessed the association between the single-nucleotide polymorphism (SNP) rs58542926 in the transmembrane 6 superfamily member 2 (TM6SF2) gene and fatty liver disease in obese youth. We genotyped the TM6SF2 rs58542926 SNP in a multiethnic cohort of 957 obese children and adolescents (42% Caucasians, 28% African Americans, 30% Hispanics). All underwent an oral glucose tolerance test, a liver panel, and a lipid profile. Of them, 454 children underwent a magnetic resonance imaging study to assess hepatic fat content and 11 underwent liver biopsy to assess the degree of disease severity. The minor allele of the rs58542926 SNP was associated with high hepatic fat content in Caucasians and African Americans (all P < 0.05), with high alanine aminotransferase levels in Hispanics (P < 0.05) and a more favorable lipoprotein profile (lower low-density lipoprotein, small dense low-density lipoprotein, and very small low-density lipoprotein) in Caucasians and Hispanics (all P < 0.05). The liver biopsy showed a higher prevalence of fibrosis (P = 0.04) and a higher nonalcoholic fatty liver disease activity score (P = 0.05) in subjects carrying the minor allele than in those homozygous for the common allele. Moreover, we observed a joint effect among the TM6SF2 rs58542926, the PNPLA3 rs738409, and the GCKR rs1260326 SNPs in determining intrahepatic fat accumulation (P < 0.05).
  
  
  CONCLUSIONS
  The rs58542926 SNP in the TM6SF2 gene is associated with pediatric nonalcoholic fatty liver disease but may confer protection against cardiovascular risk.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.|University of Milano-Bicocca, School of Medicine, Monza, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Goffredo
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego, San Diego, CA.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.affiliation: Unit of Pediatrics, Hospital of Cremona, Cremona, Italy.
authors.forename: Ebe
authors.initials: E
authors.lastname: D'Adamo
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Shaw
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Bridget
authors.initials: B
authors.lastname: Pierpont
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Mary
authors.initials: M
authors.lastname: Savoye
authors.affiliation: Department of Biostatistics, Yale School of Public Health Yale University School of Medicine, New Haven, CT.|Department of Genetics, Yale University School of Medicine, New Haven, CT.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Bale
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
mesh_terms: D000293:Adolescent; D001741:Black or African American; D002648:Child; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D008074:Lipoproteins; D008565:Membrane Proteins; C419195:TM6SF2 protein, human