Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Felix Stickel - , University of Zurich (Autor:in)
  • Philipp Lutz - , Universität Bonn (Autor:in)
  • Stephan Buch - , Medizinische Klinik und Poliklinik I (Autor:in)
  • Hans Dieter Nischalke - , Universität Bonn (Autor:in)
  • Ines Silva - , Krankenhaus Salem (Autor:in)
  • Vanessa Rausch - , Krankenhaus Salem (Autor:in)
  • Janett Fischer - , Universität Leipzig (Autor:in)
  • Karl Heinz Weiss - , Universität Heidelberg (Autor:in)
  • Daniel Gotthardt - , Universität Heidelberg (Autor:in)
  • Jonas Rosendahl - , Martin-Luther-Universität Halle-Wittenberg (Autor:in)
  • Astrid Marot - , Université de Lausanne (Autor:in)
  • Mona Elamly - , Université de Lausanne (Autor:in)
  • Marcin Krawczyk - , Universität des Saarlandes, Medical University of Warsaw (Autor:in)
  • Markus Casper - , Universität des Saarlandes (Autor:in)
  • Frank Lammert - , Universität des Saarlandes (Autor:in)
  • Thomas W.M. Buckley - , University College London (Autor:in)
  • Andrew McQuillin - , University College London (Autor:in)
  • Ulrich Spengler - , Universität Bonn (Autor:in)
  • Florian Eyer - , Technische Universität München (Autor:in)
  • Arndt Vogel - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Silke Marhenke - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Johann von Felden - , Universität Hamburg (Autor:in)
  • Henning Wege - , Universität Hamburg (Autor:in)
  • Rohini Sharma - , Imperial College London (Autor:in)
  • Stephen Atkinson - , Imperial College London (Autor:in)
  • Andre Franke - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Sophie Nehring - , Technische Universität Dresden (Autor:in)
  • Vincent Moser - , Technische Universität Dresden (Autor:in)
  • Clemens Schafmayer - , Christian-Albrechts-Universität zu Kiel (CAU) (Autor:in)
  • Laurent Spahr - , University of Geneva (Autor:in)
  • Carolin Lackner - , Medizinische Universität Graz (Autor:in)
  • Rudolf E. Stauber - , Medizinische Universität Graz (Autor:in)
  • Ali Canbay - , Ruhr-Universität Bochum (Autor:in)
  • Alexander Link - , Ruhr-Universität Bochum (Autor:in)
  • Luca Valenti - , Università degli Studi di Milano, IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano (Autor:in)
  • Jane I. Grove - , Nottingham University Hospitals NHS Trust, University of Nottingham (Autor:in)
  • Guruprasad P. Aithal - , Nottingham University Hospitals NHS Trust, University of Nottingham (Autor:in)
  • Jens U. Marquardt - , Johannes Gutenberg-Universität Mainz (Autor:in)
  • Waleed Fateen - , Nottingham University Hospitals NHS Trust, University of Nottingham (Autor:in)
  • Steffen Zopf - , Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Jean Francois Dufour - , Universität Bern (Autor:in)
  • Jonel Trebicka - , Universitätsklinikum Frankfurt (Autor:in)
  • Christian Datz - , Paracelsus Medizinischen Privatuniversität (Autor:in)
  • Pierre Deltenre - , Université de Lausanne (Autor:in)
  • Sebastian Mueller - , Krankenhaus Salem (Autor:in)
  • Thomas Berg - , Universität Leipzig (Autor:in)
  • Jochen Hampe - , Medizinische Klinik und Poliklinik I (Autor:in)
  • Marsha Y. Morgan - , University College London (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)88-102
Seitenumfang15
FachzeitschriftHepatology
Jahrgang72
Ausgabenummer1
PublikationsstatusVeröffentlicht - 1 Juli 2020
Peer-Review-StatusJa

Externe IDs

PubMed 31630428
ORCID /0000-0003-2928-015X/work/146166313

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete