The PAR4 Platelet Thrombin Receptor Variant rs773902 does not Impact the Incidence of Thrombotic or Bleeding Events in a Healthy Older Population.
Thromb Haemost
; 122(7): 1130-1138, 2022 Jul.
Article
in En
| MEDLINE
| ID: mdl-34852379
ABSTRACT
BACKGROUND:
Protease-activated receptor 4 (PAR4) is a platelet thrombin receptor important for thrombosis and a target of antiplatelet drug development. A frequently occurring single-nucleotide polymorphism (rs773902) causes a PAR4 sequence variant (NC_000019.10p.Ala120Thr) whereby platelets from Thr120-expressing individuals are hyperresponsive to PAR4 agonists versus platelets from Ala120-expressing individuals. However, whether this enhanced platelet responsiveness translates to increased thrombotic risk or decreased bleeding risk remains unknown.OBJECTIVES:
This article examines the association of rs773902 with adjudicated cardiovascular events and aspirin use in a randomized trial population of healthy older individuals.METHODS:
We analyzed 13,547 participants in the ASPirin in Reducing Events in the Elderly trial. Participants had no previous cardiovascular events at enrollment and were randomized to either 100 mg daily aspirin or placebo for a median follow-up of 4.7 years. Total genotypes were 8,761 (65%) GG (Ala120 variant), 4,303 (32%) heterozygotes, and 483 (4%) AA (Thr120 variant). Cox proportional hazard regression tested the relationship between rs773902 and thrombotic events (major adverse cardiovascular events [MACE] and ischemic stroke [IS]) and bleeding (major hemorrhage [MHEM] and intracranial bleeding [ICB]).RESULTS:
No statistically significant association was observed overall or by treatment group between rs773902 and any thrombotic or bleeding event examined. Further, there was no significant interaction between rs773902 and treatment for any of MACE, IS, MHEM, or ICB.CONCLUSION:
This post hoc analysis of a prospective cohort study suggests that, despite sensitizing platelet activation, the rs773902 PAR4 variant is not associated with thrombotic cardiovascular or bleeding events in a healthy older population.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombosis
/
Platelet Aggregation
/
Receptors, Thrombin
Type of study:
Clinical_trials
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Humans
Language:
En
Journal:
Thromb Haemost
Year:
2022
Document type:
Article
Affiliation country:
Australia