GUCY1A3 heißt das Risikogen, das die blutgerinnungshemmende Wirkung von Aspirin beeinflusst. Dies stellten jetzt Wissenschaftler des Deutschen Zentrums für Herz-Kreislauf-Forschung (DZHK)und der Klinik an der Technischen Universität München (TUM) fest.
Grund ihrer Forschungsarbeiten: Bei einem akuten Koronarsyndrom, also einer akuten Herz-Kreislauf-Erkrankung wie zum Beispiel Herzinfarkt, sind die Herzkranzgefäße entweder stark verengt oder gar komplett verschlossen. Mithilfe eines Katheters werden sie wieder geöffnet. Zudem wird eine Gefäßstütze, der sogenannte Stent, eingesetzt. Danach erhalten die Patienten Medikamente, die verhindern sollen, dass die Blutplättchen verklumpen und somit das Gefäß oder den Stent erneut verschließen. Dies können blutverdünnende Medikamente wie zum Beispiel Aspirin und sogenannte Adenosin Diphosphat (ADP)-Rezeptor-Antagonisten, meistens Clopidogrel, sein. Trotzdem kommt es vor, dass nach dem Einsetzen eines Stents immer wieder Gerinnsel auftauchen, die den Stent erneut verstopfen.
BLUTPROBEN VON FAST 1.800 PATIENTEN UNTERSUCHT
Nun haben die Forscher herausgefunden, dass Menschen, die eine Genvariante des GUCY1A3 tragen, nicht so gut auf die Gabe von Aspirin ansprechen. Auch nachdem sie dieses Medikament genommen hatten, klumpten ihre Blutplättchen stark zusammen. Nach dem Setzen eines Stents in den Herzkranzgefäßen hatten die Risikogen-Träger daher auch ein höheres Risiko, einen erneuten Gefäßverschluss zu bekommen oder sogar einen Tod durch Herzinfarkt zu erleiden.
Erstautor Dr. Thorsten Kessler vom Deutschen Herzzentrum München (DHM) und der Klinik an der TUM untersuchte für seine Studie Blutproben von knapp 1.800 Patienten. Hier beobachtete er insbesondere, ob die Genvariante GUCY1A3 vorliegt und wie ihre Blutplättchen auf die Gabe von Aspirin reagieren. Die Ergebnisse glich er dann mit bereits erfassten Daten bezüglich des Auftretens eines erneuten Gefäßverschlusses oder Herzinfarktes ab. Bei allen in den drei vorhandenen Registern „ISAR-ASPI, PLATO und UCORBIO“ erfassten Personen wurden verschlossene Herzkranzgefäße mithilfe eines Katheters wieder geweitet und ein Stent eingesetzt.
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GUCY1A3 ist bereits seit längerem als Risikogen für die koronare Herzerkrankung bekannt“, so Professor Heribert Schunkert, Direktor der Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter im DHM. „Wir wissen auch, dass es eine wichtige Rolle für die Funktion der Blutplättchen spielt.“
Denn das Gen trägt die Information für ein Protein, das eine zentrale Rolle bei der Hemmung der Blutplättchen-Aggregation spielt. An sich hemmt es sogar das Zusammenklumpen der Blutplättchen. Aber bei der hier untersuchten Variante in GUCY1A3 wird zu wenig von dem Protein gebildet, sodass die Blutplättchen stärker dazu neigen zu verklumpen. Neu ist nun, dass GUCY1A3 auch das Ansprechen auf Aspirin beeinflusst.

„Sowohl Aspirin als auch Clopidogrel haben ein gewisses Risiko nicht hundertprozentig zu wirken“, sagt Schunkert. Bei Clopidogrel liegt das an einem Stoffwechselweg, der durch eine genetische Variante so verändert sein kann, dass Clopidogrel nicht wirkt. Diese Variante lag bei den untersuchten Personen aber nicht vor. Das gleichzeitige Vorkommen beider Genvarianten sei auch höchst unwahrscheinlich, da sie nicht miteinander gekoppelt sind.
Weitere Untersuchungen sollen nun klären, ob man die Auswirkungen des Risikogens eventuell dadurch abfangen kann, dass anstatt Clopidogrel ein stärkerer ADP-Rezeptor-Antagonist, wie etwa Ticagrelor oder Prasugrel, verordnet, wird. Die Original-Veröffentlichung der Münchener ist hier nachzulesen.
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