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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2017; 11(01): 09-12
DOI: 10.1055/s-0037-1618951
Übersichtsarbeit
Schattauer GmbH

Genetik der nicht-alkoholischen Fettlebererkrankung

Genetics of fatty liver disease
M. Krawczyk
1   Klinik für Innere Medizin II, Universität des Saarlandes, Universitätsklinikum des Saarlandes, Homburg
2   Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warschau, Polen
,
F. Lammert
1   Klinik für Innere Medizin II, Universität des Saarlandes, Universitätsklinikum des Saarlandes, Homburg
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Publication History

Publication Date:
29 December 2017 (online)

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Zusammenfassung

Die nicht-alkoholische Fettlebererkrankung (NAFLD) gehört aktuell zu den häufigsten Leberkrankheiten in der Welt. Die wichtigsten exogenen Determinanten der NAFLD sind Übergewicht, Diabetes und metabolisches Syndrom. In den letzten Jahren konnte nachgewiesen werden, dass die Träger bestimmter Genvarianten nicht nur häufiger NAFLD entwickeln, sondern auch ein erhöhtes Risiko für eine fortschreitende Leberschädigung aufweisen. In Analysen sehr großer Patientenkohorten mit NAFLD konnten drei Polymorphismen, PNPLA3 p.I148M, TM6SF2 p.E167K und MBOAT7 rs641738, als sichere Risikofaktoren für die Entstehung einer Fettleber identifiziert werden. Diese Varianten sind auch mit Komplikationen der NAFLD, wie zum Beispiel Leberzirrhose und Leberkrebs, assoziiert. In dieser Übersicht werden ausgewählte Studien zu diesen Genpolymorphismen vorgestellt. Wir diskutieren ihre möglichen pathophysiologischen Mechanismen und stellen das Konzept einer genbasierten Leberkrankheit, PASH (PNPLA3-assoziierte Steatohepatitis), vor.

Summary

Non-alcoholic fatty liver disease (NAFLD) belongs to the most frequent liver disorders in the world. The exogenous risk factors for NAFLD (overweight, diabetes and metabolic syndrome) have been known for a long time. Recently it became apparent that individuals carrying specific gene variants might not only develop NAFLD more frequently but are also prone to progressive liver injury. Genomewide analyses of large cohorts of patients with NAFLD led to the identification of three prosteatotic (and profibrogenic) polymorphisms, i.e. PNPLA3 p.I148M, TM6SF2 p.E167K, and MBOAT7 rs641738. The presence of these variants also increases the risk of NAFLD complications such as liver cirrhosis and hepatocellular carcinoma. In this review, we present selected studies of each of these variants and briefly discuss their distinct functional mechanisms. Finally, we introduce the concept of PASH (PNPLA3-associated steatohepatitis) as novel genebased liver disease.

Schlüsselwörter

Adiponutrin - Fettleber - MBOAT7 - PNPLA3 - TM6SF2

Keywords

Adiponutrin - NAFLD - MBOAT7 - PNPLA3 - TM6SF2
 

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