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...
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Nature Portfolio
2017
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oai:doaj.org-article:55a3c5f524af46c0b72efc8e61276ec32021-12-02T12:30:19ZMBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals10.1038/s41598-017-04991-02045-2322https://doaj.org/article/55a3c5f524af46c0b72efc8e61276ec32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04991-0https://doaj.org/toc/2045-2322Abstract 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.Benedetta DonatiPaola DongiovanniStefano RomeoMarica MeroniMisti McCainLuca MieleSalvatore PettaSilvia MaierChiara RossoLaura De LucaEster VanniStefania GrimaudoRenato RomagnoliFabio ColliFlaminia FerriRosellina Margherita MancinaPaula IruzubietaAntonio CraxiAnna Ludovica FracanzaniAntonio GriecoStefano Ginanni CorradiniAlessio AghemoMassimo ColomboGiorgio SoardoElisabetta BugianesiHelen ReevesQuentin M. AnsteeSilvia FargionLuca ValentiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
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EN |
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Medicine R Science Q 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 Stefano Ginanni Corradini Alessio Aghemo Massimo Colombo Giorgio Soardo Elisabetta Bugianesi Helen Reeves Quentin M. Anstee Silvia Fargion Luca Valenti MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
| description |
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. |
| format |
article |
| author |
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 Stefano Ginanni Corradini Alessio Aghemo Massimo Colombo Giorgio Soardo Elisabetta Bugianesi Helen Reeves Quentin M. Anstee Silvia Fargion Luca Valenti |
| author_facet |
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 Stefano Ginanni Corradini Alessio Aghemo Massimo Colombo Giorgio Soardo Elisabetta Bugianesi Helen Reeves Quentin M. Anstee Silvia Fargion Luca Valenti |
| author_sort |
Benedetta Donati |
| title |
MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
| title_short |
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_sort |
mboat7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/55a3c5f524af46c0b72efc8e61276ec3 |
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