MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

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

Risultato della ricerca: Article

36 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)4492-
Numero di pagine10
RivistaScientific Reports
Volume7
Stato di pubblicazionePublished - 2017

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

All Science Journal Classification (ASJC) codes

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

In: Scientific Reports, Vol. 7, 2017, pag. 4492-.

Risultato della ricerca: Article

Petta, S, Craxi, A, Grimaudo, S, Aghemo, A, Anstee, QM, Colombo, M, Donati, B, Ferri, F, Mancina, RM, Rosso, C, Iruzubieta, P, De Luca, L, Grieco, A, Colli, F, Meroni, M, Maier, S, Mccain, M, Soardo, G, Romeo, S, De Luca, L, Vanni, E, Dongiovanni, P, Bugianesi, E, Corradini, SG, Fracanzani, AL, Valenti, L, Reeves, H, Miele, L, Fargion, S & Romagnoli, R 2017, 'MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals', Scientific Reports, vol. 7, pagg. 4492-.
Petta, Salvatore ; Craxi, Antonio ; Grimaudo, Stefania ; Aghemo, Alessio ; Anstee, Quentin M. ; Colombo, Massimo ; Donati, Benedetta ; Ferri, Flaminia ; Mancina, Rosellina Margherita ; Rosso, Chiara ; Iruzubieta, Paula ; De Luca, Laura ; Grieco, Antonio ; Colli, Fabio ; Meroni, Marica ; Maier, Silvia ; Mccain, Misti ; Soardo, Giorgio ; Romeo, Stefano ; De Luca, Laura ; Vanni, Ester ; Dongiovanni, Paola ; Bugianesi, Elisabetta ; Corradini, Stefano Ginanni ; Fracanzani, Anna Ludovica ; Valenti, Luca ; Reeves, Helen ; Miele, Luca ; Fargion, Silvia ; Romagnoli, Renato. / MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. In: Scientific Reports. 2017 ; Vol. 7. pagg. 4492-.
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title = "MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals",
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.",
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T1 - MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals

AU - Petta, Salvatore

AU - Craxi, Antonio

AU - Grimaudo, Stefania

AU - Aghemo, Alessio

AU - Anstee, Quentin M.

AU - Colombo, Massimo

AU - Donati, Benedetta

AU - Ferri, Flaminia

AU - Mancina, Rosellina Margherita

AU - Rosso, Chiara

AU - Iruzubieta, Paula

AU - De Luca, Laura

AU - Grieco, Antonio

AU - Colli, Fabio

AU - Meroni, Marica

AU - Maier, Silvia

AU - Mccain, Misti

AU - Soardo, Giorgio

AU - Romeo, Stefano

AU - De Luca, Laura

AU - Vanni, Ester

AU - Dongiovanni, Paola

AU - Bugianesi, Elisabetta

AU - Corradini, Stefano Ginanni

AU - Fracanzani, Anna Ludovica

AU - Valenti, Luca

AU - Reeves, Helen

AU - Miele, Luca

AU - Fargion, Silvia

AU - Romagnoli, Renato

PY - 2017

Y1 - 2017

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.

AB - 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.

KW - Multidisciplinary

UR - http://hdl.handle.net/10447/247585

UR - http://www.nature.com/srep/index.html

M3 - Article

VL - 7

SP - 4492-

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -