Dataset Information

Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.

ABSTRACT: Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0.03) but was not associated with other platelet pathways. In contrast, rs12041331 was significantly associated with on-aspirin platelet aggregation when collagen and epinephrine were used to stimulate platelet aggregation (P < 0.05 for all associations), but not ADP. The influence of PEAR1 rs12041331 on platelet aggregation is pathway-specific and is altered by aspirin at therapeutic doses, but not in a dose-dependent manner. Additional studies are needed to determine the impact of PEAR1 on cardiovascular events in aspirin-treated patients.

SUBMITTER: Backman JD

PROVIDER: S-EPMC5355965 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.

Backman J D JD Yerges-Armstrong L M LM Horenstein R B RB Newcomer S S Shaub S S Morrisey M M Donnelly P P Drolet M M Tanner K K Pavlovich M A MA O'Connell J R JR Mitchell B D BD Lewis J P JP

Clinical and translational science 20170111 2

Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly red ...[more]

PMID: 28075528

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Project description:Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel. Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models. Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07-0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06-0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08-0.72, P = 0.03 for 7-day Barthel Index, respectively]. Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone. Clinical Registration Number: 1800019911.

Dataset Information

Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.

Publications

Prospective Evaluation of Genetic Variation in Platelet Endothelial Aggregation Receptor 1 Reveals Aspirin-Dependent Effects on Platelet Aggregation Pathways.

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