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Strnad, Pavel; Buch, Stephan; Hamesch, Karim; Fischer, Janett; Rosendahl, Jonas; Schmelz, Renate; Brueckner, Stefan; Brosch, Mario; Heimes, Carolin V; Woditsch, Vivien; Scholten, David; Nischalke, Hans Dieter; Janciauskiene, Sabina; Mandorfer, Mattias; Trauner, Michael; Way, Michael J; McQuillin, Andrew; Reichert, Matthias C; Krawczyk, Marcin; Casper, Markus; Lammert, Frank; Braun, Felix; von Schönfels, Witigo; Hinz, Sebastian; [...]

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis

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  • Medientyp: E-Artikel
  • Titel: Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis
  • Beteiligte: Strnad, Pavel; Buch, Stephan; Hamesch, Karim; Fischer, Janett; Rosendahl, Jonas; Schmelz, Renate; Brueckner, Stefan; Brosch, Mario; Heimes, Carolin V; Woditsch, Vivien; Scholten, David; Nischalke, Hans Dieter; Janciauskiene, Sabina; Mandorfer, Mattias; Trauner, Michael; Way, Michael J; McQuillin, Andrew; Reichert, Matthias C; Krawczyk, Marcin; Casper, Markus; Lammert, Frank; Braun, Felix; von Schönfels, Witigo; Hinz, Sebastian; [...]
  • Erschienen: BMJ, 2019
  • Erschienen in: Gut
  • Sprache: Englisch
  • DOI: 10.1136/gutjnl-2018-316228
  • ISSN: 0017-5749; 1468-3288
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p&lt;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&lt;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 NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The 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.</jats:p></jats:sec>