1. Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
- Author
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Anna Ludovica Fracanzani, Misti Vanette McCain, Alessandro Pietrelli, Paola Dongiovanni, Chao Xing, Salvatore Petta, Antonio Grieco, Marica Meroni, Elisabetta Bugianesi, Silvia Fargion, Giorgio Soardo, Stefano Romeo, Raffaele De Francesco, Alessio Aghemo, Renato Romagnoli, Guido Baselli, Benedetta Donati, Serena Pelusi, Roberta D'Ambrosio, Luca Miele, Luca Valenti, Helen L. Reeves, Pelusi, Serena, Baselli, Guido, Pietrelli, Alessandro, Dongiovanni, Paola, Donati, Benedetta, McCain, Misti Vanette, Meroni, Marica, Fracanzani, Anna Ludovica, Romagnoli, Renato, Petta, Salvatore, Grieco, Antonio, Miele, Luca, Soardo, Giorgio, Bugianesi, Elisabetta, Fargion, Silvia, Aghemo, Alessio, D'Ambrosio, Roberta, Xing, Chao, Romeo, Stefano, De Francesco, Raffaele, Reeves, Helen Louise, and Valenti, Luca Vittorio Carlo
- Subjects
0301 basic medicine ,Male ,Candidate gene ,Apolipoprotein B ,lcsh:Medicine ,Gastroenterology ,Liver disease ,chemistry.chemical_compound ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Nonalcoholic fatty liver disease ,Sequestosome-1 Protein ,Genetic risk ,HCC ,lcsh:Science ,Multidisciplinary ,biology ,Liver Neoplasms ,Middle Aged ,3. Good health ,Cholesterol ,Hepatocellular carcinoma ,Apolipoprotein B-100 ,Female ,Aged ,Carcinoma, Hepatocellular ,Case-Control Studies ,Cholesterol, HDL ,Genetic Predisposition to Disease ,Glial Cell Line-Derived Neurotrophic Factor Receptors ,Humans ,Reproducibility of Results ,medicine.medical_specialty ,HDL ,Settore BIO/18 - GENETICA ,digestive system ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Gene ,business.industry ,lcsh:R ,Carcinoma ,nutritional and metabolic diseases ,Hepatocellular ,medicine.disease ,digestive system diseases ,030104 developmental biology ,chemistry ,NASH, HCC ,biology.protein ,lcsh:Q ,genetic ,business ,030217 neurology & neurosurgery - Abstract
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 −16), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p
- Published
- 2019