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Pathophysiologie: Genetik

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Nicht-alkoholische Fettlebererkrankung

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Zusammenfassung

Die nicht-alkoholische Fettleberkrankung („non-alcoholic fatty liver disease“, NAFLD) ist eine der häufigsten Leberkrankheiten mit steigender Inzidenz weltweit, die hauptsächlich durch die zunehmend kalorienreiche Ernährung von Kindern und Erwachsenen – kombiniert mit Bewegungsmangel – verursacht wird. Dadurch stellen die Fettlebererkrankungen eine der Hauptursachen für Zirrhose, hepatozelluläres Karzinom („hepatocellular carcinoma“, HCC) und leberbedingte Mortalität dar. Familiäre Clusterbildung und ethnische Unterschiede belegen, dass genetische Faktoren zur Fettlebererkrankung beitragen. Kürzlich wurde die Variante p.I148M des Leberenzyms PNPLA3 („patatin-like phospholipase domain-containing protein 3“) als Hauptdeterminante der nicht-alkoholischen Fettleber und Steatohepatitis sowie ihrer Folgen Zirrhose und Leberkrebs identifiziert, wobei die Steatose bei PNPLA3-assoziierter NAFLD nicht von Merkmalen des metabolischen Syndroms begleitet sein muss. PNPLA3 kodiert eine mit Lipidtröpfchen assoziierte, durch Kohlenhydrate und Fettsäuren induzierte Triacylglycerol-Lipase. Außerdem wurde gezeigt, dass eine Variante im TM6SF2-Gen überwiegend die hepatische Fettakkumulation moduliert, während eine Variante im MBOAT7-Gen die Fibroseempfänglichkeit erhöht. Die hohe Prävalenz der Risikoallele deutet darauf hin, dass zukünftig Genvarianten bei der diagnostischen Abklärung von Fettlebererkrankungen und der Überwachung der Patienten hilfreich sein könnten.

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  1. Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg, Deutschland

    Susanne N. Weber & Frank Lammert

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  1. Medizinische Klinik u. Poliklinik II, Universititätsklinikum Würzburg, ZIM, Würzburg, Bayern, Deutschland

    Andreas Geier

  2. Medizinische Klinik, Universitätsklinikum Bochum GmbH, Bochum, Deutschland

    Ali Canbay

  3. Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg, Saarland, Deutschland

    Frank Lammert

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Weber, S.N., Lammert, F. (2022). Pathophysiologie: Genetik. In: Geier, A., Canbay, A., Lammert, F. (eds) Nicht-alkoholische Fettlebererkrankung. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-62484-5_8

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