rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.
ALSPAC
Diabetes
Fibrosis
MBOAT7
NAFLD
Triglyceride
Journal
Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
21
04
2020
revised:
29
07
2020
accepted:
20
08
2020
pubmed:
4
9
2020
medline:
15
1
2022
entrez:
4
9
2020
Statut:
ppublish
Résumé
A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in 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 to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. 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], p Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.
Sections du résumé
BACKGROUND & AIMS
A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in 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 to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis.
METHODS
We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a 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], p
CONCLUSIONS
Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
LAY SUMMARY
Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.
Identifiants
pubmed: 32882372
pii: S0168-8278(20)33598-4
doi: 10.1016/j.jhep.2020.08.027
pmc: PMC7755037
pii:
doi:
Substances chimiques
Membrane Proteins
0
Acyltransferases
EC 2.3.-
MBOAT7 protein, human
EC 2.3.-
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20-30Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK061718
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111038
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061731
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : Wellcome Trust
ID : 206274/Z/17/Z
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK091601
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061734
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000058
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL060944
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000436
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK118062
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061738
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK085175
Pays : United States
Organisme : Wellcome Trust
ID : 216329/Z/19/Z
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL060919
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061737
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000006
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK061732
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114504
Pays : United States
Organisme : Medical Research Council
ID : MR/L022206/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL061019
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061713
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL060894
Pays : United States
Organisme : Medical Research Council
ID : MC UU 12015/5
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK061730
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD028016
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000100
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK045735
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA018333
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002319
Pays : United States
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR000423
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061728
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001105
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000004
Pays : United States
Investigateurs
Anita Vreugdenhil
(A)
Anna Alisi
(A)
Piotr Socha
(P)
Wojciech Jańczyk
(W)
Ulrich Baumann
(U)
Sanjay Rajwal
(S)
Indra van Mourik
(I)
Florence Lacaille
(F)
Myriam Dabbas
(M)
Deirdre A Kelly
(DA)
Valerio Nobili
(V)
Gudny Eiriksdottir
(G)
Melissa E Garcia
(ME)
Vilmundur Gudnason
(V)
Tamara B Harris
(TB)
Lauren J Kim
(LJ)
Lenore J Launer
(LJ)
Michael A Nalls
(MA)
Albert V Smith
(AV)
Jeanne M Clark
(JM)
Ruben Hernaez
(R)
W H Linda Kao
(WHL)
Braxton D Mitchell
(BD)
Alan R Shuldiner
(AR)
Laura M Yerges-Armstrong
(LM)
Ingrid B Borecki
(IB)
J Jeffrey Carr
(JJ)
Mary F Feitosa
(MF)
Jun Wu
(J)
Johannah L Butler
(JL)
Caroline S Fox
(CS)
Joel N Hirschhorn
(JN)
Udo Hoffmann
(U)
Shih-Jen Hwang
(SJ)
Joseph M Massaro
(JM)
Christopher J O'Donnell
(CJ)
Cameron D Palmer
(CD)
Dushyant V Sahani
(DV)
Elizabeth K Speliotes
(EK)
Informations de copyright
Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest C.E. reports receiving personal fees from Navitor Pharma and Novartis. The other authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
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