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SHR Neuro Krebs Kardio Lipid

Stickel, F; Lutz, P; Buch, S; Nischalke, HD; Silva, I; Rausch, V; Fischer, J; Weiss, KH; Gotthardt, D; Rosendahl, J; Marot, A; Elamly, M; Krawczyk, M; Casper, M; Lammert, F; Buckley, TWM; McQuillin, A; Spengler, U; Eyer, F; Vogel, A; Marhenke, S; von Felden, J; Wege, H; Sharma, R; Atkinson, S; Franke, A; Nehring, S; Moser, V; Schafmayer, C; Spahr, L; Lackner, C; Stauber, RE; Canbay, A; Link, A; Valenti, L; Grove, JI; Aithal, GP; Marquardt, JU; Fateen, W; Zopf, S; Dufour, JF; Trebicka, J; Datz, C; Deltenre, P; Mueller, S; Berg, T; Hampe, J; Morgan, MY.
Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers
Web of Science PubMed FullText FullText_MUG


Autor/innen der Med Uni Graz:
Lackner Karoline
Stauber Rudolf

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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 x 10(-6)) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 x 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 x 10(-26)) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 x 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 x 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.

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