@article { , title = {Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers}, abstract = {Background \& 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 PNPLA3 rs738409:G. This study explores the riskassociations 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 alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95\% 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), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95\% CI 1.54-1.88], p=1.52x10-26) 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 II diabetes mellitus 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 (p=1.72×10−4; ORallelic, 0.75; 95\% CI, 0.64–0.87). 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.}, doi = {10.1002/hep.30996}, eissn = {1527-3350}, issn = {0270-9139}, issue = {1}, journal = {Hepatology}, pages = {88-102}, publicationstatus = {Published}, publisher = {Wiley}, url = {https://nottingham-repository.worktribe.com/output/2852031}, volume = {72}, keyword = {adiponutrin, candidate genes, fibrosis, genetic risk association, genetic susceptibility, host genetics, lipotoxicity.}, year = {2020}, author = {Stickel, Felix and Lutz, Philipp and Buch, Stephan and Nischalke, Hans Dieter and Silva, Ines and Rausch, Vanessa and Fischer, Janett and Weiss, Karl Heinz and Gotthardt, Daniel and Rosendahl, Jonas and Marot, Astrid and Elamly, Mona and Krawczyk, Marcin and Casper, Markus and Lammert, Frank and Buckley, Thomas WM and McQuillin, Andrew and Spengler, Ulrich and Eyer, Florian and Vogel, Arndt and Marhenke, Silke and Felden, Johann von and Wege, Henning and Sharma, Rohini and Atkinson, Stephen and Franke, Andre and Nehring, Sophie and Moser, Vincent and Schafmayer, Clemens and Spahr, Laurent and Lackner, Carolin and Stauber, Rudolf E. and Canbay, Ali and Link, Alexander and Valenti, Luca and Grove, Jane I. and Aithal, Guruprasad P. and Marquardt, Jens U. and Fateen, Waleed and Zopf, Steffen and Dufour, Jean-Francois and Trebicka, Jonel and Datz, Christian and Deltenre, Pierre and Mueller, Sebastian and Berg, Thomas and Hampe, Jochen and Morgan, Marsha Y} }