Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease.
BACKGROUND
Clopidogrel inhibits the ADP subtype P2Y(12) receptor. Recently, polymorphisms of this receptor have been associated with different degrees of platelet aggregation in healthy volunteers and have been suggested to modulate clopidogrel response. However, the role of gene sequence variations of the P2Y(12) receptor in patients treated with clopidogrel has not yet been assessed.


METHODS
The T744C polymorphism of the P2Y(12) receptor gene was assessed in 119 patients: 36 undergoing coronary stenting receiving a 300 mg loading dose (Group A) and 83 on long-term clopidogrel (75 mg/day) treatment (Group B). Patients were divided into 2 subgroups according to the presence or absence of the C allele: carriers (CT heterozygotes and CC homozygotes) and non-carriers (TT homozygotes). Platelet aggregation, assessed by light transmittance aggregometry following ADP, collagen, TRAP and epinephrine stimuli, and platelet activation (GP IIb/IIIa activation and P-selectin expression), assessed by whole blood flow cytometry in ADP and TRAP-stimulated platelets, were performed. Platelet function was assessed at baseline and 4 and 24 h following clopidogrel loading dose in Group A and when patients where on clopidogrel treatment for at least 1 month in Group B.


RESULTS
The genotype distribution of Group A was: 22/36 (61.1%) non-carriers and 14/36 (38.9%) carriers of the C allele; Group B: 57/83 (68.7%) non-carriers and 26/83 (31.3%) carriers of the C allele. There were no differences between groups for all the assessed platelet function assays.


CONCLUSIONS
The T744C polymorphism of the P2Y(12) receptor gene does not modulate platelet response to clopidogrel either in the early or long-term phases of treatment. This specific gene polymorphism alone is therefore unlikely to be the cause of variability in individual response to antiplatelet therapy.
Angiolillo
Dominick J
DJ
Division of Cardiology, University of Florida-Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Fernandez-Ortiz
Antonio
A
Bernardo
Esther
E
Ramírez
Celia
C
Cavallari
Ugo
U
Trabetti
Elisabetta
E
Sabaté
Manel
M
Jimenez-Quevedo
Pilar
P
Hernández
Rosana
R
Moreno
Raul
R
Escaned
Javier
J
Alfonso
Fernando
F
Bañuelos
Camino
C
Costa
Marco A
MA
Bass
Theodore A
TA
Pignatti
Pier Franco
PF
Macaya
Carlos
C
D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D008565:Membrane Proteins; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine