P2RY12 gene polymorphisms and effect of clopidogrel on platelet aggregation.
Objective of this study was to assess platelet response to clopidogrel and its association with certain single nucleotide polymorphisms (SNPs) of the P2RY12 gene. Several studies have shown that patients with poor in vitro response to clopidogrel have worse outcomes after coronary interventions. Pharmacological response to clopidogrel is mediated by the P2Y12 platelet receptor, therefore, SNPs of the P2RY12 gene may account for some of the observed variability in the cardiovascular risk. Fifty patients with stable coronary heart disease, undergoing percutaneous coronary intervention were included in this study. Response to clopidogrel was analysed using light transmitted aggregometry before, and 5 days after the initation of therapy. SNPs analysed: c.-15+742C > T, c.-180+2739T > C and c.18C > T. A higher proportion of non-responders to clopidogrel were noted in carriers of 18C > T[T/T] (p = 0.05), and lower prevalence in carriers of 742C > T[T/T] (p = 0.05). Participants with 742C > T[T/T] had significantly higher change in aggregation compared to other 742C > T variants ([C/C] = 20.5 +/- 21.9%; [C/T] = 20.0 +/- 31.2%; [T/T] = 48.6 +/- 21.3%; p = 0.03). Those carrying 18C > T[T/T] had smaller change in aggregation (7.6 +/- 15.0%) compared to other variants, but the difference was not statistically significant (p = 0.15). Analysis of variance showed 18C > T[T/T] was a statistically significant predictor of poor response to antiaggregation therapy, independent from other clinical and demographic variables. There was no relation between poor response to clopidogrel and any other genetic variant. Our results suggest that 18C > T SNP of the P2RY12 gene may be an independent predictor of pharmacological response to clopidogrel. Larger prospective studies are needed to confirm this link and assess its possible clinical consequences.
"J.J. Strossmayer" University, School of Medicine, Osijek, Croatia.
Edvard
E
Galić
Luka
L
Vrbanić
Sanja
S
Kapitanović
Tina
T
Catela Ivković
Dubravka
D
Petro
Ivica
I
Vuković
Rebhi Sari
RS
Bsharat
Zvonko
Z
Milicević
Aleksandar
A
Vcev
Jure
J
Mirat
D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine