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

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@article{5b647d17c3014911b7dcea39be280930,
title = "rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis",
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.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], 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.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.",
author = "Kevin Teo and Abeysekera, {Kushala W M} and Leon Adams and Elmar Aigner and Anstee, {Quentin M} and Banales, {Jesus M} and Rajarshi Banerjee and Priyadarshi Basu and Thomas Berg and Pallav Bhatnagar and Stephan Buch and Ali Canbay and Sonia Caprio and Ankita Chatterjee and {Ida Chen}, Yii-Der and Abhijit Chowdhury and Daly, {Ann K} and Christian Datz and {de Gracia Hahn}, Dana and DiStefano, {Johanna K} and Jiawen Dong and Amedine Duret and Connor Emdin and Madison Fairey and Gerhard, {Glenn S} and Xiuqing Guo and Jochen Hampe and Matthew Hickman and Lena Heintz and Christian Hudert and Harriet Hunter and Matt Kelly and Julia Kozlitina and Marcin Krawczyk and Frank Lammert and Claudia Langenberg and Joel Lavine and Lin Li and Lim, {Hong Kai} and Rohit Loomba and Luukkonen, {Panu K} and Melton, {Phillip E} and Mori, {Trevor A} and Palmer, {Nicholette D} and Parisinos, {Constantinos A} and Pillai, {Sreekumar G} and Faiza Qayyum and Reichert, {Matthias C} and Stefan Stender and Anne Tybj{\ae}rg-Hansen and {EU-PNAFLD Investigators}",
note = "Copyright {\textcopyright} 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2021",
month = jan,
doi = "10.1016/j.jhep.2020.08.027",
language = "English",
volume = "74",
pages = "20--30",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD

T2 - A meta-analysis

AU - Teo, Kevin

AU - Abeysekera, Kushala W M

AU - Adams, Leon

AU - Aigner, Elmar

AU - Anstee, Quentin M

AU - Banales, Jesus M

AU - Banerjee, Rajarshi

AU - Basu, Priyadarshi

AU - Berg, Thomas

AU - Bhatnagar, Pallav

AU - Buch, Stephan

AU - Canbay, Ali

AU - Caprio, Sonia

AU - Chatterjee, Ankita

AU - Ida Chen, Yii-Der

AU - Chowdhury, Abhijit

AU - Daly, Ann K

AU - Datz, Christian

AU - de Gracia Hahn, Dana

AU - DiStefano, Johanna K

AU - Dong, Jiawen

AU - Duret, Amedine

AU - Emdin, Connor

AU - Fairey, Madison

AU - Gerhard, Glenn S

AU - Guo, Xiuqing

AU - Hampe, Jochen

AU - Hickman, Matthew

AU - Heintz, Lena

AU - Hudert, Christian

AU - Hunter, Harriet

AU - Kelly, Matt

AU - Kozlitina, Julia

AU - Krawczyk, Marcin

AU - Lammert, Frank

AU - Langenberg, Claudia

AU - Lavine, Joel

AU - Li, Lin

AU - Lim, Hong Kai

AU - Loomba, Rohit

AU - Luukkonen, Panu K

AU - Melton, Phillip E

AU - Mori, Trevor A

AU - Palmer, Nicholette D

AU - Parisinos, Constantinos A

AU - Pillai, Sreekumar G

AU - Qayyum, Faiza

AU - Reichert, Matthias C

AU - Stender, Stefan

AU - Tybjærg-Hansen, Anne

AU - EU-PNAFLD Investigators

N1 - Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2021/1

Y1 - 2021/1

N2 - 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], 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.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.

AB - 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], 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.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.

U2 - 10.1016/j.jhep.2020.08.027

DO - 10.1016/j.jhep.2020.08.027

M3 - Journal article

C2 - 32882372

VL - 74

SP - 20

EP - 30

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 1

ER -

ID: 61719020