Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Incidence of Hepatocellular Carcinoma in HIV/HBV-coinfected Patients on Tenofovir therapy: Relevance for Screening Strategies

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impaired cerebral microcirculation induced by ammonium chloride in rats is due to cortical adenosine release

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Micro-elimination - A path to global elimination of hepatitis C

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • EU-PNAFLD Investigators
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftJournal of Hepatology
Vol/bind74
Udgave nummer1
Sider (fra-til)20-30
Antal sider11
ISSN0168-8278
DOI
StatusUdgivet - jan. 2021

Bibliografisk note

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

ID: 61719020