Genetic Variation in PEAR1, Cardiovascular Outcomes and Effects of Aspirin in a Healthy Elderly Population
| Autor: | Mark Nelson, Christopher M. Reid, Sophia Xie, Joshua P. Lewis, Alan R. Shuldiner, Andrew Tonkin, Paul Lacaze, Rory Wolfe, John J McNeil, Galina Polekhina, Anne M. Murray, Moeen Riaz |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Platelets
Male medicine.medical_specialty Time Factors Pharmacogenomic Variants Platelet Aggregation Population Hemorrhage Receptors Cell Surface Placebo Polymorphism Single Nucleotide Risk Assessment 030226 pharmacology & pharmacy Article law.invention 03 medical and health sciences 0302 clinical medicine Double-Blind Method Randomized controlled trial Risk Factors law Internal medicine Post-hoc analysis Humans Medicine Pharmacology (medical) Prospective Studies Prospective cohort study education Stroke Aged Pharmacology Aspirin education.field_of_study business.industry Age Factors Australia medicine.disease United States Primary Prevention Cardiovascular Diseases Pharmacogenetics 030220 oncology & carcinogenesis Female business Platelet Aggregation Inhibitors Mace medicine.drug |
| Zdroj: | Clin Pharmacol Ther |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1002/cpt.1959 |
| Popis: | The platelet endothelial aggregation receptor-1 (PEAR1) rs12041331 variant has been identified as a genetic determinant of platelet aggregation in response to antiplatelet therapies, including aspirin. However, association with atherothrombotic cardiovascular events is less clear, with limited evidence from large trials. Here, we tested association of rs12041331 with cardiovascular events and aspirin use in a randomized trial population of healthy older individuals. We undertook post hoc analysis of 13,547 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, median age 74 years. Participants had no previous diagnosis of atherothrombotic cardiovascular disease at enrollment, and were randomized to either 100 mg daily low-dose aspirin or placebo for median 4.7 years follow-up. We used Cox proportional hazard regression to model the relationship between rs12041331 and the ASPREE primary cardiovascular disease (CVD) end point, and composites of major adverse cardiovascular events (MACE) and ischemic stroke (STROKE); and bleeding events; major hemorrhage (MHEM) and intracranial bleeding (ICB). We performed whole-population analysis using additive and dominant inheritance models, then stratified by treatment group. Interaction effects between genotypes and treatment group were examined. We observed no statistically significant association (P < 0.05) in the population, or by treatment group, between rs12041331 and cardiovascular or bleeding events in either model. We also found no significant interaction effects between rs12041331-A and treatment group, for CVD (P = 0.65), MACE (P = 0.32), STROKE (P = 0.56), MHEM (P = 0.59), or ICB (P = 0.56). The genetic variant PEAR1 rs12041331 is not associated with cardiovascular events in response to low-dose aspirin in a healthy elderly population. |
| Databáze: | OpenAIRE |
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