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Lookup NU author(s): Misti McCainORCiD, Dr Luca Miele, Professor Helen ReevesORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s). 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 −6 ), particularly in APOB (p = 0.047). APOB variants were associated with lower circulating triglycerides and higher HDL cholesterol (p < 0.01). A genetic risk score predicted NAFLD-HCC (OR 4.96, 3.29–7.55; p = 5.1*10 −16 ), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p < 0.05). In conclusion, rare pathogenic variants in genes involved in liver disease and cancer predisposition are associated with NAFLD-HCC development.
Author(s): Pelusi S, Baselli G, Pietrelli A, Dongiovanni P, Donati B, McCain MV, Meroni M, Fracanzani AL, Romagnoli R, Petta S, Grieco A, Miele L, Soardo G, Bugianesi E, Fargion S, Aghemo A, D'Ambrosio R, Xing C, Romeo S, De Francesco R, Reeves HL, Valenti LVC
Publication type: Article
Publication status: Published
Journal: Scientific Reports
Year: 2019
Volume: 9
Issue: 1
Online publication date: 06/03/2019
Acceptance date: 23/01/2019
Date deposited: 20/03/2019
ISSN (electronic): 2045-2322
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41598-019-39998-2
DOI: 10.1038/s41598-019-39998-2
PubMed id: 30842500
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