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Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin.

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. 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. 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.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Hall KT,Kessler T,Buring JE,Passow D,Sesso HD,Zee RYL,Ridker PM,Chasman DI,Schunkert H

doi

10.1093/eurheartj/ehz384

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

3385-3392

issue

41

eissn

0195-668X

issn

1522-9645

pii

5521149

journal_volume

40

pub_type

杂志文章,随机对照试验

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