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Genetic variant in platelet, more common in blacks, increases risk for clotting
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A genetic variation in a receptor on the surface of a platelet could help explain differences in clotting risk, according to findings from research conducted at the University of Michigan and Thomas Jefferson University.
A naturally occurring variant in the thrombin receptor Protease-Activated Receptor 4 (PAR4) appears to shift the efficacy of standard anti-platelet therapy, including aspirin and clopidogrel, or dual anti-platelet therapy combining both.
Michael Holinstat
“This work suggests that people expressing this variation of PAR4 may not be fully protected from a thrombotic event leading to a myocardial infarction and stroke,” Michael Holinstat, PhD, director of the platelet physiology and pharmacology core, University of Michigan Medical School, Ann Arbor, told Cardiology Today.
In an investigation of PAR4 signaling in platelets obtained from healthy donors and patients with CHD receiving DAPT, Holinstat and colleagues found the difference largely attributable to a variant at amino acid position 120 in PAR4 (T120A).
Individuals with a copy of the T variant demonstrated increased PAR4-mediated platelet reactivity vs. those without, independent of race. This occurred even in the presence of anti-platelet therapy.
“In the current study and other recent work published by our group, this variant of PAR4 was more highly expressed in the African-American population compared [with] the Caucasian population,” Holinstat said.
At least one copy of the gene variant was seen in 76% of blacks and 36% of whites.
With the black population known to be at increased risk for thrombotic events, even when accounting for clinical and demographic factors, the variation represents a major finding, according to the researchers.
“Identifying the genetic variant of PAR4 expressed may be a good indicator of the level of protection from platelet activation and thrombosis the physician should expect when placing the patient on anti-platelet therapy,” Holinstat said. “As the application of personalized medicine increases, new anti-platelet targets such as PAR4 may be a better approach for treating thrombotic risk in patients resistant to traditional standard-of-care approaches such as aspirin and Plavix.” – by Allegra Tiver
Disclosure: Holinstat reports no relevant financial disclosures.