1. Genetic determinants of hepatic steatosis and serum cytokeratin-18 fragment levels in Taiwanese children
- Author
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Yu-Cheng Lin, Mei-Hwei Chang, Pi-Feng Chang, and Yen-Hsuan Ni
- Subjects
Male ,0301 basic medicine ,Pediatric Obesity ,medicine.medical_specialty ,Adolescent ,Genotype ,Taiwan ,Polymorphism, Single Nucleotide ,Gastroenterology ,03 medical and health sciences ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Child ,Adaptor Proteins, Signal Transducing ,Ultrasonography ,Keratin-18 ,Hepatology ,business.industry ,Cytokeratin 18 Fragment ,Membrane Proteins ,Lipase ,medicine.disease ,Logistic Models ,030104 developmental biology ,Liver ,Multivariate Analysis ,Linear Models ,Biomarker (medicine) ,Female ,Steatosis ,business ,Body mass index ,Acyltransferases ,TM6SF2 - 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.
- Published
- 2018