Angiolillo Dominick J, Fernandez-Ortiz Antonio, Bernardo Esther, Ramírez Celia, Cavallari Ugo, Trabetti Elisabetta, Sabaté Manel, Jimenez-Quevedo Pilar, Hernández Rosana, Moreno Raul, Escaned Javier, Alfonso Fernando, Bañuelos Camino, Costa Marco A, Bass Theodore A, Pignatti Pier Franco, Macaya Carlos
Division of Cardiology, University of Florida-Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA.
Thromb Res. 2005;116(6):491-7. doi: 10.1016/j.thromres.2005.03.001. Epub 2005 Apr 20.
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.
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.
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.
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.
氯吡格雷可抑制ADP亚型P2Y(12)受体。近来，该受体的多态性与健康志愿者不同程度的血小板聚集有关，并且提示其可调节氯吡格雷的反应。然而，P2Y(12)受体基因序列变异在接受氯吡格雷治疗患者中的作用尚未得到评估。
对119例患者评估P2Y(12)受体基因的T744C多态性：36例接受冠状动脉支架置入术且负荷剂量为300mg的患者（A组），以及83例接受氯吡格雷长期（75mg/天）治疗的患者（B组）。根据是否存在C等位基因将患者分为2个亚组：携带者（CT杂合子和CC纯合子）和非携带者（TT纯合子）。采用光透比浊法在ADP刺激后、胶原刺激后、TRAP刺激后和肾上腺素刺激后评估血小板聚集，采用全血流式细胞术在ADP刺激的血小板和TRAP刺激的血小板中评估血小板活化（GP IIb/IIIa活化和P-选择素表达）。在A组氯吡格雷负荷剂量给药后基线、4小时和24小时以及B组患者接受氯吡格雷治疗至少1个月时评估血小板功能。
A组的基因型分布为：22/36（61.1%）为非携带者，14/36（38.9%）为C等位基因携带者；B组：57/83（68.7%）为非携带者，26/83（31.3%）为C等位基因携带者。在所有评估的血小板功能检测中，两组之间均无差异。
P2Y(12)受体基因的T744C多态性在治疗的早期或长期阶段均不调节血小板对氯吡格雷的反应。因此，单独这一特定基因多态性不太可能是抗血小板治疗个体反应变异性的原因。
