Genetic determinants of hepatic steatosis and serum cytokeratin-18 fragment levels in Taiwanese children
Journal
Liver International
Journal Volume
38
Journal Issue
7
Pages
1300-1307
Date Issued
2018
Author(s)
Abstract
Background/Aims: There are substantial genetic components contributing to the susceptibility of nonalcoholic fatty liver disease (NAFLD). It has recently been reported that the rs641738 C>T variant in the membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) gene increased severity of NAFLD in adults of European descent. We aimed to test the hypothesis that MBOAT7 rs641738 variant would increase hepatic steatosis and hepatocellular injury in obese children. Methods: A total of 831 obese children aged 7-15?years were recruited. Hepatic steatosis was measured by ultrasonography. Because PNPLA3 rs738409, GCKR rs780094 and TM6SF2 rs58542926 variants are known to confer susceptibility to NAFLD, we assessed the influence of MBOAT7 rs641738 on hepatic steatosis, and serum levels of CK-18 fragment (a biomarker of hepatocellular injury and apoptosis for NAFLD) after adjusting the effects of PNPLA3, GCKR and TM6SF2 polymorphisms. Results: Of the recruited obese children, 22.7% had hepatic steatosis. PNPLA3 rs738409, GCKR rs780094 and TM6SF2 rs58542926 variants were independent risk factors of hepatic steatosis and elevated ALT levels. In contrast, MBOAT7 rs641738 variants, neither heterozygous nor homozygous genotypes, were not associated with hepatic steatosis, insulin resistance, lipid levels and liver enzymes. The multiple linear regression model revealed that after adjusting for age, gender, body mass index z score, PNPLA3 rs738409 and GCKR rs780094 variants, but not MBOAT7 rs641738, were associated with serum levels of CK-18 fragment. Conclusions: The variant MBOAT7 rs641738 genotype is not associated with hepatic steatosis and serum levels of CK-18 fragment in obese Taiwanese children. ? 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
SDGs
Other Subjects
acyltransferase; cytokeratin 18; genomic DNA; o acyltransferase domain containing protein 7; unclassified drug; acyltransferase; adiponutrin, human; cytokeratin 18; GCKR protein, human; MBOAT7 protein, human; membrane protein; signal transducing adaptor protein; TM6SF2 protein, human; triacylglycerol lipase; adolescent; adult; age distribution; apoptosis; Article; body mass; child; controlled study; disease association; echography; fatty liver; female; gene frequency; genotype; human; insulin resistance; lipid level; liver cell damage; major clinical study; male; nonalcoholic fatty liver; obesity; protein blood level; real time polymerase chain reaction; sex difference; Taiwanese; waist circumference; blood; childhood obesity; complication; diagnostic imaging; genetics; liver; multivariate analysis; nonalcoholic fatty liver; risk factor; single nucleotide polymorphism; statistical model; Taiwan; Acyltransferases; Adaptor Proteins, Signal Transducing; Adolescent; Child; Female; Genotype; Humans; Keratin-18; Linear Models; Lipase; Liver; Logistic Models; Male; Membrane Proteins; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Pediatric Obesity; Polymorphism, Single Nucleotide; Risk Factors; Taiwan; Ultrasonography
Publisher
Blackwell Publishing Ltd
Type
journal article