Strnad, Pavel and Buch, Stephan and Hamesch, Karim and Fischer, Janett and Rosendahl, Jonas and Schmelz, Renate and Brueckner, Stefan and Brosch, Mario and Heimes, Carolin V. and Woditsch, Vivien and Scholten, David and Nischalke, Hans Dieter and Janciauskiene, Sabina and Mandorfer, Mattias and Trauner, Michael and Way, Michael J. and McQuillin, Andrew and Reichert, Matthias C. and Krawczyk, Marcin and Casper, Markus and Lammert, Frank and von Schoenfels, Witigo and Hinz, Sebastian and Burmeister, Greta and Hellerbrand, Claus and Teufel, Andreas and Feldman, Alexandra and Schattenberg, Joern M. and Bantel, Heike and Pathil, Anita and Demir, Muenevver and Kluwe, Johannes and Boettler, Tobias and Ridinger, Monika and Wodarz, Norbert and Soyka, Michael and Rietschel, Marcella and Kiefer, Falk and Weber, Thomas and Marhenke, Silke and Vogel, Arndt and Hinrichsen, Holger and Canbay, Ali and Schlattjan, Martin and Sosnowsky, Katharina and Sarrazin, Christoph and von Felden, Johann and Geier, Andreas and Deltenre, Pierre and Sipos, Bence and Schafmayer, Clemens and Nothnagel, Michael and Aigner, Elmar and Datz, Christian and Stickel, Felix and Morgan, Marsha Yvonne and Hampe, Jochen and Berg, Thomas and Trautwein, Christian (2019) Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis. GUT, 68 (6). pp. 1099-1107. ISSN 0017-5749, 1468-3288
Full text not available from this repository. (Request a copy)Abstract
Objective Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants (' Pi* Z' and ' Pi* S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse. Design We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi* Z and Pi* S variants was performed. Results T he Pi* Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p< 0.0001). Accordingly, the Pi* Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi* Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p< 0.0001). Correspondingly, alcohol misusers carrying the Pi* Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi* S variant was not associated with NAFLDrelated cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)). Conclusion T he Pi* Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi* S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi* Z carriers, this finding should be considered in genetic counselling of affected individuals.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MZ ALPHA-1-ANTITRYPSIN DEFICIENCY; GENOME-WIDE ASSOCIATION; TM6SF2 RS58542926; HEPATIC-FIBROSIS; HIGH PREVALENCE; DISEASE; ALPHA(1)-ANTITRYPSIN; ADULTS; ALCOHOL; PNPLA3; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Apr 2020 08:19 |
| Last Modified: | 07 Apr 2020 08:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26895 |
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