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MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

Lookup NU author(s): Misti McCainORCiD, Dr Luca Miele, Dr Paula Iruzubieta, Professor Helen ReevesORCiD, Professor Quentin AnsteeORCiD

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Abstract

Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced brosis (p < 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe brosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not signicantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33–3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07–3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.

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Author(s): Donati B, Dongiovanni P, Romeo S, Meroni M, McCain M, Miele L, Petta S, Maier S, Rosso C, De Luca L, Vanni E, Grimaudo S, Romagnoli R, Colli F, Ferri F, Mancina R, Iruzubieta P, Craxi A, Fracanzani A, Grieco A, Corradini S, Aghemo A, Colombo M, Soardo G, Bugianesi E, Reeves H, Anstee Q, Fargion S, Valenti L

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2017

Volume: 7

Online publication date: 03/07/2017

Acceptance date: 23/05/2017

Date deposited: 11/07/2017

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41598-017-04991-0

DOI: 10.1038/s41598-017-04991-0

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