| Title: | rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis |
| Journal: | Journal of Hepatology |
| Published: | 31 Aug 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32882372/ |
| DOI: | https://doi.org/10.1016/j.jhep.2020.08.027 |
| URL: | http://www.journal-of-hepatology.eu/article/S0168827820335984/pdf |
Publication 13692
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Abstract
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.</p>
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.</p>
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 = 4.8×10-5) and diagnosis of NAFLD (odds ratio [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 = 1.5×10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.</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.</p>
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.</p>
10 Keywords
- Acyltransferases
- Alanine Transaminase
- Drug Discovery
- Genetic Predisposition to Disease
- Humans
- Liver
- Liver Cirrhosis
- Membrane Proteins
- Non-alcoholic Fatty Liver Disease
- Polymorphism, Single Nucleotide
112 Authors
- Kevin Teo
- Kushala W.M. Abeysekera
- Leon Adams
- Elmar Aigner
- Quentin M. Anstee
- Jesus M. Banales
- Rajarshi Banerjee
- Priyadarshi Basu
- Thomas Berg
- Pallav Bhatnagar
- Stephan Buch
- Ali Canbay
- Sonia Caprio
- Ankita Chatterjee
- Yii-Der Ida Chen
- Abhijit Chowdhury
- Ann K. Daly
- Christian Datz
- Dana de Gracia Hahn
- Johanna K. DiStefano
- Jiawen Dong
- Amedine Duret
- EU-PNAFLD Investigators
- Anita Vreugdenhil
- Anna Alisi
- Piotr Socha
- Wojciech Jańczyk
- Ulrich Baumann
- Sanjay Rajwal
- Indra van Mourik
- Florence Lacaille
- Myriam Dabbas
- Deirdre A. Kelly
- Valerio Nobili
- Connor Emdin
- Madison Fairey
- Glenn S. Gerhard
- GOLD Consortium
- Gudny Eiriksdottir
- Melissa E. Garcia
- Vilmundur Gudnason
- Tamara B. Harris
- Lauren J. Kim
- Lenore J. Launer
- Michael A. Nalls
- Albert V. Smith
- Jeanne M. Clark
- Ruben Hernaez
- W.H. Linda Kao
- Braxton D. Mitchell
- Alan R. Shuldiner
- Laura M. Yerges-Armstrong
- Ingrid B. Borecki
- J. Jeffrey Carr
- Mary F. Feitosa
- Jun Wu
- Johannah L. Butler
- Caroline S. Fox
- Joel N. Hirschhorn
- Udo Hoffmann
- Shih-Jen Hwang
- Joseph M. Massaro
- Christopher J. O'Donnell
- Cameron D. Palmer
- Dushyant V. Sahani
- Elizabeth K. Speliotes
- Xiuqing Guo
- Jochen Hampe
- Matthew Hickman
- Lena Heintz
- Christian Hudert
- Harriet Hunter
- Matt Kelly
- Julia Kozlitina
- Marcin Krawczyk
- Frank Lammert
- Claudia Langenberg
- Joel Lavine
- Lin Li
- Hong Kai Lim
- Rohit Loomba
- Panu K. Luukkonen
- Phillip E. Melton
- Trevor A. Mori
- Nicholette D. Palmer
- Constantinos A. Parisinos
- Sreekumar G. Pillai
- Faiza Qayyum
- Matthias C. Reichert
- Stefano Romeo
- Jerome I. Rotter
- Yu Ri Im
- Nicola Santoro
- Clemens Schafmayer
- Elizabeth K. Speliotes
- Stefan Stender
- Felix Stickel
- Christopher D. Still
- Pavel Strnad
- Kent D. Taylor
- Anne Tybjærg-Hansen
- Giuseppina Rosaria Umano
- Mrudula Utukuri
- Luca Valenti
- Lynne E. Wagenknecht
- Nicholas J. Wareham
- Richard M. Watanabe
- Julia Wattacheril
- Hanieh Yaghootkar
- Hannele Yki-Järvinen
- Kendra A. Young
- Jake P. Mann
1 Application
| Application ID | Title |
|---|---|
| 9914 | Determining the Outcomes of People with Liver Disease |
Enabling scientific discoveries that improve human health