MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

Benedetta Donati, Paola Dongiovanni, Stefano Romeo, Marica Meroni, Misti McCain, Luca Miele, Salvatore Petta, Silvia Maier, Chiara Rosso, Laura De Luca, Ester Vanni, Stefania Grimaudo, Renato Romagnoli, Fabio Colli, Flaminia Ferri, Rosellina Margherita Mancina, Paula Iruzubieta, Antonio Craxi, Anna Ludovica Fracanzani, Antonio Grieco & 9 others Stefano Ginanni Corradini, Alessio Aghemo, Massimo Colombo, Giorgio Soardo, Elisabetta Bugianesi, Helen Reeves, Quentin M. Anstee, Silvia Fargion, Luca Valenti

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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 fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly 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.

Original languageEnglish
Article number4492
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Hepatocellular Carcinoma
Alleles
Fibrosis
Alcoholic Liver Diseases
3' Untranslated Regions
Chronic Hepatitis C
Non-alcoholic Fatty Liver Disease
Carcinogenesis
Prospective Studies
Liver

ASJC Scopus subject areas

  • General

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MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. / Donati, Benedetta; Dongiovanni, Paola; Romeo, Stefano; Meroni, Marica; McCain, Misti; Miele, Luca; Petta, Salvatore; Maier, Silvia; Rosso, Chiara; De Luca, Laura; Vanni, Ester; Grimaudo, Stefania; Romagnoli, Renato; Colli, Fabio; Ferri, Flaminia; Mancina, Rosellina Margherita; Iruzubieta, Paula; Craxi, Antonio; Fracanzani, Anna Ludovica; Grieco, Antonio; Corradini, Stefano Ginanni; Aghemo, Alessio; Colombo, Massimo; Soardo, Giorgio; Bugianesi, Elisabetta; Reeves, Helen; Anstee, Quentin M.; Fargion, Silvia; Valenti, Luca.

In: Scientific Reports, Vol. 7, No. 1, 4492, 01.12.2017.

Research output: Contribution to journalArticle

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, RM, Iruzubieta, P, Craxi, A, Fracanzani, AL, Grieco, A, Corradini, SG, Aghemo, A, Colombo, M, Soardo, G, Bugianesi, E, Reeves, H, Anstee, QM, Fargion, S & Valenti, L 2017, 'MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals', Scientific Reports, vol. 7, no. 1, 4492. https://doi.org/10.1038/s41598-017-04991-0
Donati, Benedetta ; Dongiovanni, Paola ; Romeo, Stefano ; Meroni, Marica ; McCain, Misti ; Miele, Luca ; Petta, Salvatore ; Maier, Silvia ; Rosso, Chiara ; De Luca, Laura ; Vanni, Ester ; Grimaudo, Stefania ; Romagnoli, Renato ; Colli, Fabio ; Ferri, Flaminia ; Mancina, Rosellina Margherita ; Iruzubieta, Paula ; Craxi, Antonio ; Fracanzani, Anna Ludovica ; Grieco, Antonio ; Corradini, Stefano Ginanni ; Aghemo, Alessio ; Colombo, Massimo ; Soardo, Giorgio ; Bugianesi, Elisabetta ; Reeves, Helen ; Anstee, Quentin M. ; Fargion, Silvia ; Valenti, Luca. / MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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AU - Donati, Benedetta

AU - Dongiovanni, Paola

AU - Romeo, Stefano

AU - Meroni, Marica

AU - McCain, Misti

AU - Miele, Luca

AU - Petta, Salvatore

AU - Maier, Silvia

AU - Rosso, Chiara

AU - De Luca, Laura

AU - Vanni, Ester

AU - Grimaudo, Stefania

AU - Romagnoli, Renato

AU - Colli, Fabio

AU - Ferri, Flaminia

AU - Mancina, Rosellina Margherita

AU - Iruzubieta, Paula

AU - Craxi, Antonio

AU - Fracanzani, Anna Ludovica

AU - Grieco, Antonio

AU - Corradini, Stefano Ginanni

AU - Aghemo, Alessio

AU - Colombo, Massimo

AU - Soardo, Giorgio

AU - Bugianesi, Elisabetta

AU - Reeves, Helen

AU - Anstee, Quentin M.

AU - Fargion, Silvia

AU - Valenti, Luca

PY - 2017/12/1

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N2 - 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 fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly 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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