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MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495751/ https://www.ncbi.nlm.nih.gov/pubmed/28674415 http://dx.doi.org/10.1038/s41598-017-04991-0 |
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author | 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 |
author_facet | 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 |
author_sort | Donati, Benedetta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5495751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54957512017-07-07 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 Sci Rep Article 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. Nature Publishing Group UK 2017-07-03 /pmc/articles/PMC5495751/ /pubmed/28674415 http://dx.doi.org/10.1038/s41598-017-04991-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 |
title | MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
title_full | MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
title_fullStr | MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
title_full_unstemmed | MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
title_short | MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
title_sort | mboat7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495751/ https://www.ncbi.nlm.nih.gov/pubmed/28674415 http://dx.doi.org/10.1038/s41598-017-04991-0 |
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