Genetics of platelet reactivity in normal, healthy individuals

Background: The Platelet Function Analyzer-100 (PFA-100) is widely used to measure platelet reactivity in whole blood under high shear. Objective: To characterize the genetic component of platelet reactivity among normal individuals, using the PFA-100. Methods: We compared baseline platelet reactivity with sex, age, platelet count, hematocrit, plasma von Willebrand factor antigen (VWF:Ag), and alleles of seven candidate genes: integrin subunits alpha 2 (ITGA2) and beta 3 (ITGB3), platelet glycoproteins GPIb alpha (GP1BA) and GPVI (GP6), purinogenic receptors (P2RY1 and P2RY12) and cyclooxygenase-1 (COX1). Results: Based on linear and logistic regression models, we report an inverse correlation between baseline closure time (CT) initiated by collagen plus epinephrine (CEPI) and plasma VWF:Ag level, ITGA2 807T and P2RY1 893C, and an inverse correlation between baseline CT initiated by collagen plus adenosine diphosphate (CADP) and P2RY1 893C or GP1BA -5C. Conclusions: These results indicate that genetic polymorphisms in ITGA2 and P2RY1 combine with plasma VWF:Ag levels to modulate baseline platelet reactivity in response to collagen plus EPI, while genetic differences in P2RY1 and GP1BA significantly effect platelet responses to collagen plus ADP. Our results demonstrate that the PFA-100 can be used to evaluate the effects of genetic predictors of platelet function.