rs641738C>T near MBOAT7 promotes steatosis, NASH, fibrosis and hepatocellular carcinoma in non-alcoholic fatty liver disease: a meta-analysis
By
Kevin Teo,
Kushala WM Abeysekera,
Leon Adams,
Elmar Aigner,
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,
Christian Datz,
Dana de Gracia Hahn,
Johanna K DiStefano,
Jiawen Dong,
Amedine Duret,
EU-PNAFLD Investigators,
Connor Emdin,
Madison Fairey,
Glenn S Gerhard,
GOLD Consortium,
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 Luukkonen,
Philip E Melton,
Trevor A Mori,
Constantinos A Parisinos,
Nicholette D Palmer,
Sreekumar G Pillai,
Faiza Qayyum,
Matthias C Reichert,
Stefano Romeo,
Jerome Rotter,
Yu Ri Im,
Nicola Santoro,
Clemens Schafmayer,
Elizabeth K Speliotes,
Stefan Stender,
Felix Stickel,
Christopher D Still,
Pavel Strnad,
Kent D Taylor,
Anne Tybjaerg-Hansen,
Giuseppina Rosaria Umano,
Mrudula Utukuri,
Luca Valenti,
Lynne E Wagenknecht,
Eric R Gamazon,
Richard M Watanabe,
Julia Wattacheril,
Hanieh Yaghootkar,
Hannele Yki-Jarvinen,
Kendra A. Young,
Jake P Mann
Posted 04 Dec 2019
medRxiv DOI: 10.1101/19013623
A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. Therefore, we aimed to establish whether rs641738 is a risk factor for NAFLD through meta-analysis. Data from 131,096 participants (7,692 with liver biopsies and 45,419 with imaging) was included in the meta-analysis. The minor T-allele of rs641738C>T was associated with higher liver fat on CT/MRI using an additive genetic model (+0.05 standard deviations [95% CI: 0.01 - 0.09], p=0.025), and with an increased risk of NAFLD (per-allele OR: 1.09 [95% CI: 1.01 - 1.17]), nonalcoholic steatohepatitis (OR: 1.11 [95% CI: 1.02 - 1.21]), advanced fibrosis (OR: 1.14 [95% CI: 1.05 - 1.23]), and hepatocellular carcinoma (OR: 1.43 [95% CI: 1.22 - 1.67]) in adults with NAFLD. Sub-group analysis did not demonstrate a difference in Caucasians and non-Caucasians. Rs641738C>T was not associated with markers of insulin resistance but was associated with higher risk of stroke in the UK Biobank. These data validate rs641738C>T near MBOAT7 as a risk factor for the development, activity, and stage of NAFLD including hepatocellular carcinoma.
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