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Cardiovasc Res. 2019 Feb 14. pii: cvz015. doi: 10.1093/cvr/cvz015. [Epub ahead of print]

Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention.

Author information

1
Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
2
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V., Partner Site Munich Heart Alliance, Munich, Germany.
3
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
4
Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, The Netherlands.
5
Cardiology Department, St. Antonius Hospital, Nieuwegein, The Netherlands.
6
Division of Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
7
Division of Cardiovascular Health and Disease, University of Cincinnati Heart, Lung & Vascular Institute, Cincinnati, OH, USA.
8
I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
9
Innere Medizin III: Kardiologie, Angiologie und Pneumologie, Universität Heidelberg, and DZHK e.V., Partner Site Heidelberg, Heidelberg, Germany.
10
Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
11
University Heart Center Lübeck, Lübeck, Germany.
12
DZHK e.V., Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
13
Charité-University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
14
Department of Periodontology and Synoptic Dentistry, Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Berlin, Germany.
15
TIMI Study Group, Brigham and Women's Hospital, Boston, MA, USA.
16
Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.
17
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield, UK.
18
Institute of Cardiovascular Science, Faculty of Population Health Sciences, London, UK.
19
Health Data Research UK and Institute of Health Informatics, University College London, London, UK.

Abstract

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 (>203 AU⋅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.

KEYWORDS:

Genetic variation ; Genome-wide association studies ; On-aspirin platelet reactivity ; Platelet aggregation; Stent thrombosis

PMID:
30768153
DOI:
10.1093/cvr/cvz015

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