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Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin.
- Source :
-
European heart journal [Eur Heart J] 2019 Nov 01; Vol. 40 (41), pp. 3385-3392. - Publication Year :
- 2019
-
Abstract
- Aims: Efficacy of aspirin in primary prevention of cardiovascular disease (CVD) may be influenced by a common allele in guanylate cyclase GUCY1A3, which has been shown to modify platelet function and increase CVD risk.<br />Methods and Results: We investigated whether homozygotes of the GUCY1A3 rs7692387 risk (G) allele benefited from aspirin in two long-term, randomized placebo-controlled trials of aspirin in primary CVD prevention: the Women's Genome Health Study (WGHS, N = 23 294) and a myocardial infarction (MI, N = 550) and stroke (N = 382) case-control set from the Physician's Health Study (PHS, N = 22 071). Bleeding risk was evaluated in the WGHS. In the placebo group of the WGHS, the GUCY1A3 risk (G) allele was confirmed to increase CVD risk [hazard ratio 1.38; 95% confidence interval (CI) 1.08-1.78; P = 0.01]. Random-effects meta-analysis of the WGHS and PHS revealed that aspirin reduced CVD events among risk allele homozygotes [G/G: odds ratio (OR) 0.79; 95% CI 0.65-0.97; P = 0.03] but increased CVD events among non-risk allele carriers (e.g. G/A: OR 1.39; 95% CI 1.03-1.87; P = 0.03) thus implying an interaction between genotype stratum and aspirin intake (Pinteraction = 0.01). Bleeding associated with aspirin increased in all genotype groups, with higher risks in heterozygotes.<br />Conclusion: In two randomized placebo-controlled trials in the setting of primary prevention, aspirin reduced the incidence of CVD events in individuals homozygous for the GUCY1A3 risk (G) allele, whereas heterozygote individuals had more events when taking aspirin.<br /> (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Female
Genetic Predisposition to Disease epidemiology
Genetic Predisposition to Disease genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide genetics
Primary Prevention
Aspirin adverse effects
Aspirin therapeutic use
Cardiovascular Diseases drug therapy
Cardiovascular Diseases epidemiology
Cardiovascular Diseases genetics
Cardiovascular Diseases prevention & control
Coronary Artery Disease epidemiology
Coronary Artery Disease genetics
Soluble Guanylyl Cyclase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-9645
- Volume :
- 40
- Issue :
- 41
- Database :
- MEDLINE
- Journal :
- European heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 31228190
- Full Text :
- https://doi.org/10.1093/eurheartj/ehz384