eprintid: 10088511
rev_number: 24
eprint_status: archive
userid: 608
dir: disk0/10/08/85/11
datestamp: 2020-01-07 07:53:39
lastmod: 2021-11-30 23:03:30
status_changed: 2020-01-07 07:53:39
type: article
metadata_visibility: show
creators_name: Kessler, T
creators_name: Wolf, B
creators_name: Eriksson, N
creators_name: Kofink, D
creators_name: Mahmoodi, BK
creators_name: Rai, H
creators_name: Tragante, V
creators_name: Akerblom, A
creators_name: Becker, RC
creators_name: Bernlochner, I
creators_name: Bopp, R
creators_name: James, S
creators_name: Katus, HA
creators_name: Mayer, K
creators_name: Munz, M
creators_name: Nordio, F
creators_name: O'Donoghue, ML
creators_name: Sager, HB
creators_name: Sibbing, D
creators_name: Solakov, L
creators_name: Storey, RF
creators_name: Wobst, J
creators_name: Asselbergs, FW
creators_name: Byrne, RA
creators_name: Erdmann, J
creators_name: Koenig, W
creators_name: Laugwitz, K-L
creators_name: ten Berg, JM
creators_name: Wallentin, L
creators_name: Kastrati, A
creators_name: Schunkert, H
title: Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
ispublished: pub
divisions: UCL
divisions: B02
divisions: DD4
keywords: On-aspirin platelet reactivity, Genetic variation, Stent thrombosis, Genome-wide association studies, Platelet aggregation
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2019-08-01
date_type: published
publisher: OXFORD UNIV PRESS
official_url: https://doi.org/10.1093/cvr/cvz015
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1682979
doi: 10.1093/cvr/cvz015
lyricists_name: Asselbergs, Folkert
lyricists_id: FASSE08
actors_name: Asselbergs, Folkert
actors_id: FASSE08
actors_role: owner
full_text_status: public
publication: Cardiovascular Research
volume: 115
number: 10
pagerange: 1512-1518
pages: 7
issn: 1755-3245
citation:        Kessler, T;    Wolf, B;    Eriksson, N;    Kofink, D;    Mahmoodi, BK;    Rai, H;    Tragante, V;                                                                                                 ... Schunkert, H; + view all <#>        Kessler, T;  Wolf, B;  Eriksson, N;  Kofink, D;  Mahmoodi, BK;  Rai, H;  Tragante, V;  Akerblom, A;  Becker, RC;  Bernlochner, I;  Bopp, R;  James, S;  Katus, HA;  Mayer, K;  Munz, M;  Nordio, F;  O'Donoghue, ML;  Sager, HB;  Sibbing, D;  Solakov, L;  Storey, RF;  Wobst, J;  Asselbergs, FW;  Byrne, RA;  Erdmann, J;  Koenig, W;  Laugwitz, K-L;  ten Berg, JM;  Wallentin, L;  Kastrati, A;  Schunkert, H;   - view fewer <#>    (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 <https://doi.org/10.1093/cvr%2Fcvz015>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10088511/1/GUCY_aspi_MS_revision%231_20181219_manuscript.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/10088511/7/Figures.pdf