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

Thorsten Kessler, Bernhard Wolf, Niclas Eriksson, Daniel Kofink, Bakhtawar K. Mahmoodi, Himanshu Rai, Vinicius Tragante, Axel Åkerblom, Richard C. Becker, Isabell Bernlochner, Roman Bopp, Stefan James, Hugo A. Katus, Katharina Mayer, Matthias Munz, Francesco Nordio, Michelle L. O'Donoghue, Hendrik B. Sager, Dirk Sibbing, Linda SolakovRobert F. Storey, Jana Wobst, Folkert W. Asselbergs, Robert A. Byrne, Jeanette Erdmann, Wolfgang Koenig, Karl Ludwig Laugwitz, Jurrien M. Ten Berg, Lars Wallentin, Adnan Kastrati, Heribert Schunkert*

*Corresponding author for this work
7 Citations (Scopus)


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) AUâ 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 AUâ 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.

Original languageEnglish
JournalCardiovascular Research
Issue number10
Pages (from-to)1512-1518
Number of pages7
Publication statusPublished - 2019

Research Areas and Centers

  • Research Area: Medical Genetics


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