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 alpha2 (ITGA2) and beta3 (ITGB3), platelet glycoproteins GPIbalpha (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.
Kunicki
T J
TJ
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. tomk@scripps.edu
Williams
S A
SA
Salomon
D R
DR
Harrison
P
P
Crisler
P
P
Nakagawa
P
P
Mondala
T S
TS
Head
S R
SR
Nugent
D J
DJ
D000367:Age Factors; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics*; D010979:Platelet Function Tests; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058472:Receptors, Purinergic P2Y1; D012737:Sex Factors; D014841:von Willebrand Factor / Q000032:analysis
D039421:Integrin alpha2; D008562:Membrane Glycoproteins; C546382:P2RY1 protein, human; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; C094990:adhesion receptor; D014841:von Willebrand Factor