Zoheir Naguib, Abd Elhamid Samah, Abulata Nelly, El Sobky Mehry, Khafagy Doaa, Mostafa Amr
Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Blood Coagul Fibrinolysis. 2013 Jul;24(5):525-31. doi: 10.1097/MBC.0b013e32835e98bf.
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.
血小板在血栓形成的病理生理学中起核心作用。二磷酸腺苷(ADP)作为血小板激活的激动剂发挥关键作用。P2Y12 ADP受体的基因多态性可能会影响ADP对该受体的激活或患者对血小板抑制剂的反应。本研究共纳入80名参与者,其中40例被诊断为急性冠状动脉综合征,40例年龄和性别匹配的健康志愿者作为对照。评估了(服用氯吡格雷之前和之后1周)血小板聚集情况,并使用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法对P2Y12受体基因的T744C基因多态性进行基因分型。患者服用氯吡格雷之前血小板聚集范围为54%-183%,服用之后为4%-113%。对候选基因的基因分型显示,72.5%的患者有野生等位基因(TT),而27.5%有C等位基因(杂合子CT、纯合子CC)。相反,97.5%的对照有野生等位基因(TT),而2.5%有C等位基因(杂合子CT、纯合子CC)。我们的研究揭示了P2Y12 ADP受体基因的T744C多态性与血小板反应性之间的关联。在该位置携带C等位基因与ADP诱导的血小板激活反应增加相关。