Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 03 2019
Historique:
received: 05 09 2018
accepted: 23 01 2019
entrez: 8 3 2019
pubmed: 8 3 2019
medline: 22 10 2020
Statut: epublish

Résumé

Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p = 0.024), and likely pathogenic variants (p = 1.9*10

Identifiants

pubmed: 30842500
doi: 10.1038/s41598-019-39998-2
pii: 10.1038/s41598-019-39998-2
pmc: PMC6403344
doi:

Substances chimiques

APOB protein, human 0
Apolipoprotein B-100 0
Cholesterol, HDL 0
GFRA1 protein, human 0
Glial Cell Line-Derived Neurotrophic Factor Receptors 0
SQSTM1 protein, human 0
Sequestosome-1 Protein 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3682

Subventions

Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom

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Auteurs

Serena Pelusi (S)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Translational Medicine, Department of Transfusion Medicine and Hepatology, Milan, Italy.

Guido Baselli (G)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Alessandro Pietrelli (A)

Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Paola Dongiovanni (P)

Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Benedetta Donati (B)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Misti Vanette McCain (MV)

Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK.

Marica Meroni (M)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Anna Ludovica Fracanzani (AL)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Renato Romagnoli (R)

Department of Surgical Sciences, Liver Transplantation Center, University of Turin, Turin, Italy.

Salvatore Petta (S)

Section of Gastroenterology, DIBIMIS, University of Palermo, 90127, Palermo, Italy.

Antonio Grieco (A)

Internal Medicine and Gastroenterology Area, Fondazione Policlinico Universitario A. Gemelli, Catholic University of Rome, 00168, Rome, Italy.

Luca Miele (L)

Internal Medicine and Gastroenterology Area, Fondazione Policlinico Universitario A. Gemelli, Catholic University of Rome, 00168, Rome, Italy.

Giorgio Soardo (G)

Clinic of Internal Medicine-Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.

Elisabetta Bugianesi (E)

Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.

Silvia Fargion (S)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Alessio Aghemo (A)

Division of Gastroenterology and Hepatology Unit, Humanitas Research Hospital and Humanitas University, Rozzano (MI), Italy.

Roberta D'Ambrosio (R)

"A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.

Chao Xing (C)

McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Stefano Romeo (S)

Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Cardiology Department, University of Gothenburg, Gothenburg, Sweden.
Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Raffaele De Francesco (R)

Istituto Nazionale di Genetica Molecolare (INGM), Romeo ed Enrica Invernizzi, Bioinformatic group, Milan, Italy.

Helen Louise Reeves (HL)

Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK.
Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.

Luca Vittorio Carlo Valenti (LVC)

Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. luca.valenti@unimi.it.
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. luca.valenti@unimi.it.
Translational Medicine, Department of Transfusion Medicine and Hepatology, Milan, Italy. luca.valenti@unimi.it.

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