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

Kevin Teo, Kushala W M Abeysekera, Matthew Hickman, Jake P Mann, et al.

Research output: Contribution to journalArticle (Academic Journal)


Background & AimsA common genetic variant near MBOAT7 (rs641738C>T) has been previouslyassociated with hepatic fat and advanced histology in non-alcoholic fatty liverdisease (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.
MethodsWe performed meta-analysis of studies with data on the association betweenrs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and populationlevel data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.
ResultsData from 1,066,175 participants (9,688 with liver biopsies) across 42 studieswere included in the meta-analysis. rs641738C>T was associated with higherliver 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.
ConclusionOur study validates rs641738C>T near MBOAT7 as a risk factor for thepresence and severity of NAFLD in individuals of European descent.
Original languageEnglish
JournalJournal of Hepatology
Publication statusAccepted/In press - 21 Aug 2020

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