Strnad, Pavel, Buch, Stephan, Hamesch, Karim ORCID: 0000-0002-1702-2746, Fischer, Janett, Rosendahl, Jonas, Schmelz, Renate, Brueckner, Stefan, Brosch, Mario, Heimes, Carolin V., Woditsch, Vivien, Scholten, David, Nischalke, Hans Dieter, Janciauskiene, Sabina, Mandorfer, Mattias ORCID: 0000-0003-2330-0017, Trauner, Michael ORCID: 0000-0002-1275-6425, Way, Michael J., McQuillin, Andrew ORCID: 0000-0003-1567-2240, Reichert, Matthias C., Krawczyk, Marcin ORCID: 0000-0002-0113-0777, Casper, Markus, Lammert, Frank, von Schoenfels, Witigo, Hinz, Sebastian, Burmeister, Greta, Hellerbrand, Claus, Teufel, Andreas, Feldman, Alexandra, Schattenberg, Joern M., Bantel, Heike, Pathil, Anita, Demir, Muenevver, Kluwe, Johannes, Boettler, Tobias ORCID: 0000-0002-1195-055X, Ridinger, Monika, Wodarz, Norbert, Soyka, Michael, Rietschel, Marcella, Kiefer, Falk, Weber, Thomas, Marhenke, Silke, Vogel, Arndt, Hinrichsen, Holger, Canbay, Ali ORCID: 0000-0001-6069-7899, Schlattjan, Martin, Sosnowsky, Katharina, Sarrazin, Christoph, von Felden, Johann, Geier, Andreas, Deltenre, Pierre, Sipos, Bence, Schafmayer, Clemens, Nothnagel, Michael ORCID: 0000-0001-8305-7114, Aigner, Elmar, Datz, Christian, Stickel, Felix, Morgan, Marsha Yvonne, Hampe, Jochen ORCID: 0000-0002-2421-6127, 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). S. 1099 - 1108. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-3288

Full text not available from this repository.

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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Strnad, PavelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buch, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamesch, KarimUNSPECIFIEDorcid.org/0000-0002-1702-2746UNSPECIFIED
Fischer, JanettUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosendahl, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmelz, RenateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brueckner, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brosch, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heimes, Carolin V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woditsch, VivienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholten, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nischalke, Hans DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janciauskiene, SabinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mandorfer, MattiasUNSPECIFIEDorcid.org/0000-0003-2330-0017UNSPECIFIED
Trauner, MichaelUNSPECIFIEDorcid.org/0000-0002-1275-6425UNSPECIFIED
Way, Michael J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McQuillin, AndrewUNSPECIFIEDorcid.org/0000-0003-1567-2240UNSPECIFIED
Reichert, Matthias C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krawczyk, MarcinUNSPECIFIEDorcid.org/0000-0002-0113-0777UNSPECIFIED
Casper, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammert, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Schoenfels, WitigoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hinz, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burmeister, GretaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hellerbrand, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teufel, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feldman, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schattenberg, Joern M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bantel, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pathil, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demir, MuenevverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluwe, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boettler, TobiasUNSPECIFIEDorcid.org/0000-0002-1195-055XUNSPECIFIED
Ridinger, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wodarz, NorbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soyka, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiefer, FalkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marhenke, SilkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogel, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hinrichsen, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canbay, AliUNSPECIFIEDorcid.org/0000-0001-6069-7899UNSPECIFIED
Schlattjan, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sosnowsky, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sarrazin, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Felden, JohannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geier, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deltenre, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sipos, BenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schafmayer, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothnagel, MichaelUNSPECIFIEDorcid.org/0000-0001-8305-7114UNSPECIFIED
Aigner, ElmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Datz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stickel, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, Marsha YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hampe, JochenUNSPECIFIEDorcid.org/0000-0002-2421-6127UNSPECIFIED
Berg, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trautwein, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-146407
DOI: 10.1136/gutjnl-2018-316228
Journal or Publication Title: Gut
Volume: 68
Number: 6
Page Range: S. 1099 - 1108
Date: 2019
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-3288
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MZ ALPHA-1-ANTITRYPSIN DEFICIENCY; GENOME-WIDE ASSOCIATION; TM6SF2 RS58542926; HEPATIC-FIBROSIS; HIGH PREVALENCE; DISEASE; ALPHA(1)-ANTITRYPSIN; ADULTS; ALCOHOL; PNPLA3Multiple languages
Gastroenterology & HepatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14640

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item