Komplexe Genetik des ischämischen Hirninfarktes

Zusammenfassung

Der Hirninfarkt ist ätiologisch und genetisch sehr heterogen. Diese Übersicht soll ausschließlich die komplexe Genetik ischämischer Hirninfarkte darstellen. In den letzten Jahren hat die Genetik seltener monogener Formen des Schlaganfalls enorme Fortschritte gemacht, ohne dass diese Kenntnisse jedoch eine größere Bedeutung für die häufigen polyfaktoriellen Formen des ischämischen Hirninfarktes erlangt haben. Letztere sind durch das Zusammenwirken von erblichen Faktoren und Umweltfaktoren verursacht. Voraussetzung für die Erforschung der komplexen genetischen Grundlagen ist eine genaue klinische Charakterisierung und Unterteilung der Patienten in ätiologisch möglichst homogene Untergruppen. Hierzu wird meist die TOAST-Klassifikation verwendet. Die am weitesten verbreitete Methode zur Untersuchung komplexer genetischer Krankheiten ist die Assoziationsstudie im Fall-/KontrollDesign. Von der isländischen DeCode Gruppe wurde kürzlich in großen Studienpopulationen eine Assoziation zwischen Polymorphismen in den Genen PDE4D und ALOX5AP und ischämischem Hirninfarkt gefunden. Im Kompetenznetz Schlaganfall (Subnetz “Genetische Schlaganfallforschung”, Projekt A3) haben wir ebenfalls eine große Stichprobe von Patienten mit ischämischem Hirninfarkt gesammelt und eine Replikationsstudie der isländischen Ergebnisse in einer zentraleuropäischen Population durchgeführt.

Summary

Stroke is etiologically and genetically heterogenous. This review will exclusively discuss the complex genetics of ischemic stroke. In recent years enormous progress has been made regarding the rare monogenic forms of stroke. However, this knowledge has contributed very little towards the understanding of the more frequent polyfactorial types of ischemic stroke. The latter are caused bya complex synergy of genetic and environmental factors. The exact clinical characterization and classification of stroke patients into etiologically defined homogeneous subgroups is a prerequisite for the genetic investigation. For this purpose, the TOAST classification is widely used. The most common method for the investigation of complex genetic diseases are association studies ina case/control design. Recently, the Icelandic DeCode group found associations between polymorphisms in the genes PDE4D and ALOX5AP and ischemic stroke. Within the competence net stroke (project A3), we have collected a large number of patients with ischemic stroke and performeda replication study of the Icelandic results in a central European population.

Schlüsselwörter

Ischämischer Hirninfarkt - Genetik - PDE4D - ALOX5AP

Keywords

Ischemic stroke - genetics - PDE4D - ALOX5AP

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