eCite Digital Repository

rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis

Citation

Teo, K and Abeysekera, KWM and Adams, L and Aigner, E and Anstee, QM and Banales, JM and Banerjee, R and Basu, P and Berg, T and Bhatnagar, P and Buch, S and Canbay, A and Caprio, S and Chatterjee, A and Chen, Y-DI and Chowdhury, A and Daly, AK and Datz, C and Hahn, DG and DiStefano, JK and Dong, J and Duret, A and Emdin, C and Fairey, M and Gerhard, GS and Guo, X and Hampe, J and Hickman, M and Heintz, L and Hudert, C and Hunter, H and Kelly, M and Kozlitina, J and Krawczyk, M and Lammert, F and Langenberg, C and Lavine, J and Li, L and Lim, HK and Loomba, R and Luukkonen, PK and Melton, PE and Mori, TA and Palmer, ND and Parisinos, CA and Pillai, SG and Qayyum, F and Reichert, MC and Romeo, S and Rotter, JI and Im, YR and Santoro, N and Schafmayer, C and Speliotes, EK and Stender, S and Stickel, F and Still, CD and Strnad, P and Taylor, KD and Tybjaerg-Hansen, A and Umano, GR and Utukuri, M and Valenti, L and Wagenknecht, LE and Wareham, NJ and Watanabe, RM and Wattacheril, J and Yaghootkar, H and Yki-Jarvinen, H and Young, KA and Mann, JP, EU-PNAFLD Investigators, GOLD Consortium, rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis, Journal of Hepatology, 74, (1) pp. 20-30. ISSN 0168-8278 (2020) [Refereed Article]


Preview
PDF
832Kb
  

Copyright Statement

Copyright 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY license

DOI: doi:10.1016/j.jhep.2020.08.027

Abstract

Background & aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.

Methods: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.

Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.

Conclusion: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

Item Details

Item Type:Refereed Article
Keywords:ALSPAC, MBOAT7, NAFLD, diabetes, fibrosis, triglyceride
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Gene mapping
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:141375
Year Published:2020
Web of Science® Times Cited:30
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-10-16
Last Modified:2022-08-19
Downloads:13 View Download Statistics

Repository Staff Only: item control page