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Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
Tech Univ Munich, Deutsch Herzzentrum Munchen, Klin Herz & Kreislauferkrankungen, Munich, Germany;Deutsch Zentrum Herz Kreislauf Forsch DZHK eV, Partner Site Munich Heart Alliance, Munich, Germany.ORCID iD: 0000-0003-3326-1621
Tech Univ Munich, Deutsch Herzzentrum Munchen, Klin Herz & Kreislauferkrankungen, Munich, Germany;Deutsch Zentrum Herz Kreislauf Forsch DZHK eV, Partner Site Munich Heart Alliance, Munich, Germany.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.ORCID iD: 0000-0002-2152-4343
Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
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2019 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 115, no 10, p. 1512-1518Article in journal (Refereed) Published
Abstract [en]

Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2019. Vol. 115, no 10, p. 1512-1518
Keywords [en]
On-aspirin platelet reactivity, Genetic variation, Stent thrombosis, Genome-wide association studies, Platelet aggregation
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-397295DOI: 10.1093/cvr/cvz015ISI: 000492854700015PubMedID: 30768153OAI: oai:DiVA.org:uu-397295DiVA, id: diva2:1372743
Funder
EU, FP7, Seventh Framework Programme, HEALTH-F2-2013-601456EU, European Research Council, ERC 261053Available from: 2019-11-25 Created: 2019-11-25 Last updated: 2019-11-25Bibliographically approved

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Eriksson, NiclasÅkerblom, AxelJames, StefanWallentin, Lars

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