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GUCY1A3 is the name of the risk gene that influences the anticoagulant effect of aspirin. This has now been established by scientists at the German Centre for Cardiovascular Research (DZHK) and the Clinic at the Technical University of Munich (TUM).

Reason for their research work: In an acute coronary syndrome, meaning an acute cardiovascular disease such as a heart attack, the coronary vessels are either severely constricted or even completely blocked. They are opened again with the help of a catheter. In addition, vascular support, the so-called stent, is inserted. The patients are then given medication to prevent the blood platelets from clumping and thus re-blocking the vessel or stent. These can be blood-thinning drugs such as aspirin and so-called adenosine diphosphate (ADP) receptor antagonists, usually clopidogrel. Nevertheless, after the insertion of a stent, clotting can occur all the time and clot the stent again.

BLOOD SAMPLES FROM ALMOST 1,800 PATIENTS EXAMINED

Now, the researchers have discovered that people who carry a gene variant of GUCY1A3 do not react so well to aspirin. Even after they took the drug, their platelets clotted together. After placing a stent in the coronary arteries, the carriers of the risk gene therefore also had a higher risk of getting a new vascular occlusion or even dying from a heart attack.

Lead author Dr. Thorsten Kessler from the German Heart Centre Munich (DHM) and the TUM Clinic examined blood samples from almost 1,800 patients for his study. In particular, he paid attention to whether the gene variant GUCY1A3 is present and how the blood platelets react to aspirin. He then compared the results with data already collected on the occurrence of a new vascular occlusion or heart attack. In all three registers “ISAR-ASPI, PLATO and UCORBIO” examined people’s closed coronary vessels were widened again with the help of a catheter and a stent was inserted.

TOO LITTLE PROTEIN

GUCY1A3 has long been known as a risk gene for coronary heart disease,” said Professor Heribert Schunkert, Director of the Clinic for Adult Heart and Circulatory Diseases at the DHM. “We also know that it plays an important role in platelet function.”

The gene carries the information for a protein that plays a central role in inhibiting platelet aggregation. In itself, it even inhibits the clumping of platelets. However, in the GUCY1A3 variant investigated here, too little of the protein is formed, so that the platelets have a greater tendency to clump together. What is new is that GUCY1A3 also impacts the response to aspirin.

Prof. Dr. Heribert Schunkert, ©Deutsches Herzzentrum München

“Both aspirin and clopidogrel have a certain risk of not being 100% effective,” said Schunkert. In clopidogrel, this is due to a metabolic pathway that can be altered by a genetic variant in such a way that clopidogrel does not work. However, this variant was not present in the investigated people. The simultaneous occurrence of both gene variants is also highly unlikely as they are not coupled.

Further investigations are meant to clarify whether the effects of the risk gene can possibly be prevented by prescribing a stronger ADP receptor antagonist, such as ticagrelor or prasugrel, instead of clopidogrel. The original Munich publication can be found here.