title: P2Y12 receptor gene polymorphism and antiplatelet effect of clopidogrel in patients with coronary artery disease after coronary stenting.
abstract: Platelets have a central role in the pathophysiology of thrombosis. Adenosine diphosphate (ADP) plays a pivotal role as an agonist of platelet activation. Genetic polymorphisms of the P2Y12 ADP receptor might influence the activation of this receptor by ADP or the response of patients to platelet inhibitors. The present study was conducted on a total number of 80 participants, 40 patients were diagnosed with acute coronary syndrome and 40 sex and aged-matched healthy volunteers were included as controls. Platelet aggregation was assessed (before and 1 week after clopidogrel administration) and genotyping of the T744C genetic polymorphism of P2Y12 receptor gene was carried out using the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method. Platelet aggregation of the patients had a range of 54-183% before clopidogrel administration and had a range of 4-113% after its administration. Genotyping of the candidate gene revealed that 72.5% of the patients had a wild allele (TT), whereas 27.5% had a C allele (heterozygous CT, homozygous CC). On the contrary, 97.5% of controls had a wild allele (TT), whereas 2.5% had a C allele (heterozygous CT, homozygous CC). Our study elicited an association between the T744C polymorphism of the P2Y12 ADP receptor gene and platelet reactivity. Carrying the C allele at this position is associated with an increased platelet activation response to ADP.
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Naguib
authors.initials: N
authors.lastname: Zoheir
authors.forename: Samah
authors.initials: S
authors.lastname: Abd Elhamid
authors.forename: Nelly
authors.initials: N
authors.lastname: Abulata
authors.forename: Mehry
authors.initials: M
authors.lastname: El Sobky
authors.forename: Doaa
authors.initials: D
authors.lastname: Khafagy
authors.forename: Amr
authors.initials: A
authors.lastname: Mostafa
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics / Q000601:surgery*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine