P2RY12 Gene Polymorphisms and Effect of Clopidogrel on Platelet Aggregation

Edvard Galić, Luka Vrbanić, Sanja Kapitanović, Tina Catela Ivković, Dubravka Petro, Ivica Vuković, Rebhi Sari Bsharat, Zvonko Miličević, Aleksandar Včev, Jure Mirat


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.


coronary heart disease, percutaneous coronary intervention, platelet function, P2Y12 receptor, P2RY12 gene, antiplatelet therapy

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