Identifizierung von Risikogenen für den Herzinfarkt durch genomweite Assoziationsstudien

Summary

Myocardial infarction (MI) shows a strong heritability. For a long time the identification of responsible genes has been rather unsuccessful. However, with the advent of genome wide association studies (GWAS) using DNA-array technology a number of significant loci for MI have been identified which were widely replicated. Interestingly, only a small fraction of the hitherto identified genes is also associated with classical risk factors for MI such as hypercholesterolemia or diabetes. Therefore it can be concluded that the MI risk mediated by the newly identified genes involves a number of novel pathophysiological mechanisms.

This review summarizes the present state of knowledge in the field and tries to give a perspective on how these findings can be translated into clinical practice and further scientific discovery. Special consideration is given to the association of MI risk with genetic variants in the hemostatic system.

Zusammenfassung

Der Herzinfarkt hat eine starke erbliche Komponente. Die Aufschlüsselung der verantwortlichen Gene gestaltete sich allerdings lange Zeit sehr schwierig. Erst genomweite Assoziationsstudien (GWAS), die mittels DNA-Chip Technologie ermöglicht wurden, konnten eine größere Zahl von genetischen Varianten identifiziert, die inzwischen in zahlreichen Kohorten belastbar repliziert wurden. Interessanterweise wirkt nur ein kleiner Teil der bisher identifizierten Varianten über klassische Risikofaktoren (z. B. Lipide). Die Ergebnisse der GWAS lassen daher auf zahlreiche bislang unbekannte Pathomechanismen für den Herzinfarkt schließen.

Diese Arbeit fasst den Stand dieser Forschung zusammen und gibt einen Ausblick, wie die neuen Erkenntnisse diagnostisch und therapeutisch nutzbar gemacht werden können. Eine besondere Berücksichtigung findet der Zusammenhang von genetischen Varianten in Genen des hämostatischen Systems mit dem Herzinfarkt.

Keywords

Myocardial infarction - genetic variants - genome-wide-association-studies

Schlüsselwörter

Herzinfarkt - genetische Varianten - genom weite-Assoziationsstudien

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