Why the study?
The structural basis for PAR4 activation and the location of its ligand binding site were unknown.
Does the PAR4 Leu310 allele reduce the risk of venous thromboembolism compared to the Pro310 allele?
Population
Individuals from the INVENT consortium multi-ancestry GWAS meta-analysis and laboratory models of PAR4
Comparison
PAR4 Leu310 allele vs Pro310 allele and PAR4 mutants vs wild-type
Design
Preclinical structural, modeling, and signaling study with a multi-ancestry GWAS meta-analysis
Authors
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Informs PAR4-targeted antithrombotic design; leaves open clinical translation pending validation.
Does the PAR4 Leu310 allele reduce the risk of venous thromboembolism compared to the Pro310 allele?
The PAR4 Leu310 allele is associated with a reduced risk of venous thromboembolism, supported by structural evidence that extracellular loop 3 rigidity is essential for PAR4 activation.
Xu et al. (2020) studied this question.
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