rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis
K. Teo, Kushala Abeysekera, Leon A. Adams, Elmar Aigner, Quentin M. Anstee, Jesús M. Bañales, Rajarshi Banerjee, P. Basu, Thomas Berg, Pallav Bhatnagar, Stephan Buch, Ali Canbay, Sonia Caprio, A Chatterjee, Yii‐Der Ida Chen, Abhijit Chowdhury, Ann K. Daly, Christian Datz, Dana de Gracia Hahn, Johanna K. DiStefano, Jiawen Dong, Amédine Duret, Anita Vreugdenhil, Anna Alisi, Piotr Socha, Wojciech Jańczyk, Ulrich Baumann, Sanjay Rajwal, Indra van Mourik, Florence Lacaille, M. Dabbas, Déirdre Kelly, Valério Nobili, Connor A. Emdin, Madison Fairey, Glenn S. Gerhard, Guðný Eiríksdóttir, Melissa E. Garcia, Vilmundur Guðnason, Tamara B. Harris, Lauren J. Kim, Lenore J. Launer, Michael A. Nalls, Albert V. Smith, Jeanne M. Clark, Rubén Hernáez, Wei-Tang 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 E. Lavine, Lin Li, Hong Kai Lim, Rohit Loomba, Panu K. Luukkonen, Phillip E. Melton, Trevor A. Mori, Nicholette D. Palmer, Constantinos A. Parisinos, Sreekumar Pillai, Faiza Qayyum, Matthias 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
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: ). 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.