Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet activation response to ADP.
OBJECTIVE
The platelet ADP receptors P2Y1 and P2Y12 play a pivotal role in platelet aggregation. There is marked interindividual variation in platelet response to ADP. We studied whether genetic variants in the P2Y1 or P2Y12 genes affect platelet response to ADP.


RESULTS
The P2Y1 and P2Y12 genes were screened for polymorphisms. Associations between selected polymorphisms and the platelet response to ADP (0.1, 1.0, and 10 micromol/L), assessed by whole blood flow cytometric measurement of fibrinogen binding to activated glycoprotein IIb-IIIa, were then determined in 200 subjects. Five polymorphisms were found in the P2Y1 gene and 11 in the P2Y12 gene. All polymorphisms were silent. A P2Y1 gene dimorphism, 1622AG, was associated with a significant (P=0.007) effect on platelet ADP response, with a greater response in carriers of the G allele (frequency 0.15). The effect was seen at all concentrations of ADP but greatest at 0.1 mumol/L ADP, where the response in GG homozygotes was on average 130% higher than that seen in AA homozygotes (P=0.006).


CONCLUSIONS
A common genetic variant at the P2Y1 locus is associated with platelet reactivity to ADP. This genotype effect partly explains the interindividual variation in platelet response to ADP and may have clinical implications with regard to thrombotic risk.
Hetherington
Simon L
SL
Department of Cardiovascular Sciences, University of Leicester, United Kingdom.
Singh
Ravi K
RK
Lodwick
David
D
Thompson
John R
JR
Goodall
Alison H
AH
Samani
Nilesh J
NJ
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D015539:Platelet Activation / Q000235:genetics*; D010974:Platelet Aggregation / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin; D000244:Adenosine Diphosphate