急性冠脉综合征患者血小板功能与CYP2C19及GPIaC807T基因多态性的相关性研究

Polymorphisms of Glycoprotein Ia C807T and CYP2C19 and the Association With Platelet Function in Patients With the Acute Coronary Syndrome

目的本研究探讨急性冠脉综合征患者血小板功能与CYP2C19和GPIa C807T基因多态性的相关关系,以及不同基因型患者对抗血小板治疗效果的差异。方法入选282例确诊的急性冠脉综合征(Acute Coronary Syndrome,ACS)患者,测定细胞色素P450(CYP)2C19和血小板膜糖蛋白(platelet membrane Glycoprotein,GP)Ia C807T基因型,以及花生四烯酸(Arachidonic Acid,AA)和二磷酸腺苷(Adenosine Diphosphate,ADP)诱导的血小板聚集率。结果抗血小板治疗前,携带GPIa C807T等位T基因的ACS患者血小板聚集率高于CC基因型患者,而CYP2C19不同基因型患者间的血小板聚集率差异无统计学意义。双联抗血小板治疗对CYP2C19慢代谢型的效果较快代谢型和中等代谢型差;而对GPIa C807T CC基因型患者相比携带T等位基因的患者治疗效果更显著。结论 GPIa C807T的基因多态性可能是影响急性冠脉综合症发生和抗血小板疗效差异的另一因素。携带GPIa T等位基因的CYP2C19慢代谢型ACS患者可能需要更积极的抗血栓治疗方案。

Objective In the current study,we explored the relationship between Cytochrome P450（CYP）2C19,glycoprotein Ia（GPIa）C807T polymorphisms and platelet function; and the differences to dual antiplatelet treatment among different genotypes of acute coronary syndrome（ACS）patients. Methods We conducted a study in 282 patients diagnosed with ACS. The CYP2C19 and GPIa C807 T genotypes of patients were determined,and platelet aggregation and plasma concentrations of α-granule membrane protein（GMP-140） were assessed following stimulation with arachidonic acid and adenosine diphosphate. Results Before dual antiplatelet treatment（DAPT）,platelet aggregation was significantly lower in individuals with the CC group than in those with the T allele; but there there was no difference among three kinds of metabolism phenotypes of CYP2C19. DAPT reduced platelet aggregation in all three genotypes of GPIa C807 T,and patients carrying the CC genotype were more sensitive to DAPT than those with the T allele. In patients of poor metabolizers of CYP2C19,platelet aggregation after DAPT was higher than the individuals of expensive metalolizers and intermediate metalolizers. Conclusion The GPIa C807 T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele and the poor metabolizers of CYP2C19 may help to identify a group of patients who need more aggressive antithrombotic treatment.