Kessler, T;
Wolf, B;
Eriksson, N;
Kofink, D;
Mahmoodi, BK;
Rai, H;
Tragante, V;
... Schunkert, H; + view all
(2019)
Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention.
Cardiovascular Research
, 115
(10)
pp. 1512-1518.
10.1093/cvr/cvz015.
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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.
| Type: | Article |
|---|---|
| Title: | Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/cvr/cvz015 |
| Publisher version: | https://doi.org/10.1093/cvr/cvz015 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | On-aspirin platelet reactivity, Genetic variation, Stent thrombosis, Genome-wide association studies, Platelet aggregation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10088511 |
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