Tello-Montoliu Antonio, Jover Eva, Marín Francisco, Bernal Agustina, Lozano María L, Sánchez-Vega Beatriz, Pastor Francisco J, Hurtado José A, Valdés Mariano, Vicente Vicente, Rivera José
Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Rev Esp Cardiol (Engl Ed). 2012 Mar;65(3):219-26. doi: 10.1016/j.recesp.2011.07.013. Epub 2011 Nov 23.
CYP2C192 and CYP2C1917 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome.
Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay.
Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and 17 allele carriers (P=.048). No significant difference was found between CYP2C192 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up.
Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables.
CYP2C192和CYP2C1917等位基因似乎导致了氯吡格雷代谢的异质性。本研究的目的是评估CYP2C192和17等位基因携带情况的表型-基因型关系，并在非ST段抬高急性冠状动脉综合征的未选择人群中，探讨这些多态性在急性事件6个月随访时的临床影响。
分别招募40例冠状动脉支架置入术后12个月接受双联抗血小板治疗的稳定急性冠状动脉综合征患者用于第一个和第二个目的，以及493例连续的未选择的非ST段抬高急性冠状动脉综合征患者。通过二磷酸腺苷和凝血酶受体激活肽诱导的光学聚集法以及使用流式细胞术测量血管扩张剂刺激的磷蛋白磷酸化来评估血小板反应性。用TaqMan分析法定型。
只有血管扩张剂刺激的磷蛋白磷酸化测量检测到野生型受试者与CYP2C192（P = 0.020）和17等位基因携带者（P = 0.048）之间在服用氯吡格雷时血小板反应性存在显著差异。在6个月随访时，CYP2C192（[风险比（95%置信区间）：1（0.94 - 1.55）]，P = 0.984）或17（[风险比（95%置信区间）：0.93（0.61 - 1.43）]，P = 0.753）等位基因携带与不良事件的发生之间未发现显著差异。
尽管CYP2C19基因型与服用氯吡格雷时血小板反应性的变化有关，但它没有显著的临床影响。急性冠状动脉综合征的预后可能受到众多变量的影响。
