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Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.
Stickel, Felix; Lutz, Philipp; Buch, Stephan; Nischalke, Hans Dieter; Silva, Ines; Rausch, Vanessa; Fischer, Janett; Weiss, Karl Heinz; Gotthardt, Daniel; Rosendahl, Jonas; Marot, Astrid; Elamly, Mona; Krawczyk, Marcin; Casper, Markus; Lammert, Frank; Buckley, Thomas W M; McQuillin, Andrew; Spengler, Ulrich; Eyer, Florian; Vogel, Arndt; Marhenke, Silke; von Felden, Johann; Wege, Henning; Sharma, Rohini; Atkinson, Stephen; Franke, Andre; Nehring, Sophie; Moser, Vincent; Schafmayer, Clemens; Spahr, Laurent; Lackner, Carolin; Stauber, Rudolf E; Canbay, Ali; Link, Alexander; Valenti, Luca; Grove, Jane I; Aithal, Guruprasad P; Marquardt, Jens U; Fateen, Waleed; Zopf, Steffen; Dufour, Jean-Francois; Trebicka, Jonel; Datz, Christian; Deltenre, Pierre; Mueller, Sebastian; Berg, Thomas; Hampe, Jochen; Morgan, Marsha Y.
Afiliación
  • Stickel F; Department of Gastroenterology and Hepatology, University Hospital of Zürich, Switzerland.
  • Lutz P; Department of Internal Medicine I, University of Bonn, Bonn, Germany.
  • Buch S; Medical Department 1, University Hospital Dresden, TU Dresden, Germany.
  • Nischalke HD; Department of Internal Medicine I, University of Bonn, Bonn, Germany.
  • Silva I; Department of Internal Medicine and Center for Alcohol Research, Salem Medical Center University Hospital Heidelberg, Heidelberg, Germany.
  • Rausch V; Department of Internal Medicine and Center for Alcohol Research, Salem Medical Center University Hospital Heidelberg, Heidelberg, Germany.
  • Fischer J; Division of Hepatology, Clinic and Polyclinic for Gastroenterology, Hepatology, Infectiology and Pneumology, University Clinic Leipzig, Leipzig, Germany.
  • Weiss KH; Department of Internal Medicine IV, Medical University of Heidelberg, Germany.
  • Gotthardt D; Department of Internal Medicine IV, Medical University of Heidelberg, Germany.
  • Rosendahl J; Department of Gastroenterology, University Hospital Halle/Saale, Germany.
  • Marot A; Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.
  • Elamly M; Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.
  • Krawczyk M; Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
  • Casper M; Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
  • Lammert F; Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
  • Buckley TWM; Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
  • McQuillin A; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK.
  • Spengler U; Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, UK.
  • Eyer F; Department of Internal Medicine I, University of Bonn, Bonn, Germany.
  • Vogel A; Department of Clinical Toxicology, Klinikum Rechts der Isar, Technical University of Munich, Germany.
  • Marhenke S; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
  • von Felden J; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
  • Wege H; First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Sharma R; First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Atkinson S; Department of Metabolism, Digestion & Reproduction, Division of Surgery and Cancer, Imperial College London, London, UK.
  • Franke A; Department of Metabolism, Digestion & Reproduction, Division of Surgery and Cancer, Imperial College London, London, UK.
  • Nehring S; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
  • Moser V; Medical Department 1, University Hospital Dresden, TU Dresden, Germany.
  • Schafmayer C; Medical Department 1, University Hospital Dresden, TU Dresden, Germany.
  • Spahr L; Department of Visceral and Thoracic Surgery, Kiel University, Kiel, Germany.
  • Lackner C; Departments of Gastroenterology and Hepatology, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
  • Stauber RE; Institute of Pathology, Medical University of Graz, Austria.
  • Canbay A; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.
  • Link A; Ruhr-Universität Bochum, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
  • Valenti L; Ruhr-Universität Bochum, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
  • Grove JI; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
  • Aithal GP; Translational Medicine - Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy.
  • Marquardt JU; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • Fateen W; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
  • Zopf S; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • Dufour JF; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
  • Trebicka J; Department of Medicine I, Johannes Gutenberg-Universität Mainz, Mainz, Germany.
  • Datz C; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • Deltenre P; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
  • Mueller S; Medical Department 1, University of Erlangen-Nuremberg, Germany.
  • Berg T; University Clinic for Visceral Surgery and Medicine, Inselspital, University of Berne, Berne, Switzerland.
  • Hampe J; Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany.
  • Morgan MY; Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private Medical University of Salzburg, Oberndorf, Austria.
Hepatology ; 72(1): 88-102, 2020 07.
Article en En | MEDLINE | ID: mdl-31630428
BACKGROUND AND AIMS: Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10-6 ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10-4 ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10-26 ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10-23 ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (ORallelic , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10-4 ). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Carcinoma Hepatocelular / Alcoholismo / 17-Hidroxiesteroide Deshidrogenasas / Cirrosis Hepática Alcohólica / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Hepatology Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Variación Genética / Carcinoma Hepatocelular / Alcoholismo / 17-Hidroxiesteroide Deshidrogenasas / Cirrosis Hepática Alcohólica / Neoplasias Hepáticas Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Hepatology Año: 2020 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos