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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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Teo, K, Abeysekera, KWM, Adams, L, Aigner, E, Anstee, QM, Banales, JM, Banerjee, R, Basu, P, Berg, T, Bhatnagar, P, Buch, S, Canbay, A, Caprio, S, Chatterjee, A, Chen, Y-DI, Chowdhury, A, Daly, AK, Datz, C, Hahn, DG, DiStefano, JK, Dong, J, Duret, A, Emdin, C, Fairey, M, Gerhard, GS, Guo, X, Hampe, J, Hickman, M, Heintz, L, Hudert, C, Hunter, H, Kelly, M, Kozlitina, J, Krawczyk, M, Lammert, F, Langenberg, C, Lavine, J, Li, L, Lim, HK, Loomba, R, Luukkonen, PK, Melton, PE ORCID: 0000-0003-4026-2964, Mori, TA, Palmer, ND, Parisinos, CA, Pillai, SG, Qayyum, F, Reichert, MC, Romeo, S, Rotter, JI, Im, YR, Santoro, N, Schafmayer, C, Speliotes, EK, Stender, S, Stickel, F, Still, CD, Strnad, P, Taylor, KD, Tybjaerg-Hansen, A, Umano, GR, Utukuri, M, Valenti, L, Wagenknecht, LE, Wareham, NJ, Watanabe, RM, Wattacheril, J, Yaghootkar, H, Yki-Jarvinen, H, Young, KA and Mann, JP 2020 , 'rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis' , Journal of Hepatology , doi: 10.1016/j.jhep.2020.08.027.

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Abstract

Background & aims: 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. 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. Methods: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed 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=4.8x10-5) 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.Conclusion: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

Item Type: Article
Authors/Creators:Teo, K and Abeysekera, KWM and Adams, L and Aigner, E and Anstee, QM and Banales, JM and Banerjee, R and Basu, P and Berg, T and Bhatnagar, P and Buch, S and Canbay, A and Caprio, S and Chatterjee, A and Chen, Y-DI and Chowdhury, A and Daly, AK and Datz, C and Hahn, DG and DiStefano, JK and Dong, J and Duret, A and Emdin, C and Fairey, M and Gerhard, GS and Guo, X and Hampe, J and Hickman, M and Heintz, L and Hudert, C and Hunter, H and Kelly, M and Kozlitina, J and Krawczyk, M and Lammert, F and Langenberg, C and Lavine, J and Li, L and Lim, HK and Loomba, R and Luukkonen, PK and Melton, PE and Mori, TA and Palmer, ND and Parisinos, CA and Pillai, SG and Qayyum, F and Reichert, MC and Romeo, S and Rotter, JI and Im, YR and Santoro, N and Schafmayer, C and Speliotes, EK and Stender, S and Stickel, F and Still, CD and Strnad, P and Taylor, KD and Tybjaerg-Hansen, A and Umano, GR and Utukuri, M and Valenti, L and Wagenknecht, LE and Wareham, NJ and Watanabe, RM and Wattacheril, J and Yaghootkar, H and Yki-Jarvinen, H and Young, KA and Mann, JP
Keywords: ALSPAC, MBOAT7, NAFLD, diabetes, fibrosis, triglyceride
Journal or Publication Title: Journal of Hepatology
Publisher: Elsevier Science Bv
ISSN: 0168-8278
DOI / ID Number: 10.1016/j.jhep.2020.08.027
Copyright Information:

Copyright 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY license

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