血小板二磷酸腺苷受体H2单体型与阿司匹林抗血小板功能学监测关联的研究

目的探讨血小板二磷酸腺苷受体(P2Y12)H2单体型对中国老年汉族患者阿司匹林抑制血小板聚集功能及血小板计数的影响。方法入选北京万寿路地区服用阿司匹林老年汉族患者431例,使用美国Sequenom系统单核苷酸多态性分型技术对P2Y12H1/H2单体型进行鉴定。采用花生四烯酸诱导的光比浊和血栓弹力图法、二磷酸腺苷诱导的光比浊和血栓弹力图法、血小板活化标记物血小板激活复合物1、CD62P等血小板功能检测,对P2Y12H2单体型与血小板计数及阿司匹林抗血小板聚集功能进一步行相关分析。结果 431例患者中,P2Y12H1/H1基因型285例,H1/H2基因型136例,H2/H2基因型10例。H1/H1、H1/H2、H2/H2基因型血小板计数分别为(216.09±58.76)×109/L,(195.06±55.16)×109/L,(164.90±46.12)×109/L,差异有统计学意义(P<0.01)。H1/H2+H2/H2与H1/H1比较,经年龄、性别校正后,多因素回归分析仍提示血小板计数与H2相关联(P=0.005)。结论 P2Y12H2单体型对阿司匹林的抗血小板作用无明显影响。携带P2Y12H2单体型患者的血小板计数明显低于H1型患者,提示P2Y12H2单体型可能是正常人群血小板计数低下的一个基因学标志。

Correlation between P2Y_(12) H2 haplotype and aspirin antiplatelet function

Objective To study the effect of P2Y12 H2 haplotype on aspirin antiplatelet function and platelet count in elderly Chinese Han patients.Methods Four hundred and thirty-one elderly Chinese Han patients on aspirin therapy were included in this study.P2Y12 H1/H2 haplotypes were identified using the mononucleotide polymormophism typing technique of US Sequenom System.Platelet activation markers PAC-1and CD62Pwere detected by arachidonic acid-induced light transmittance aggregation(LTA)and thrombelastography(TEG),adenosine diphosphate-induced LTA and TEG,respectively.Correlation of P2Y12 H2 haplotype with aspirin antiplatelet function and platelet count was analyzed.Results Of the 431patients,285(66.1%)showed P2Y12 H1/H1 haplotype,136(31.6%)showed P2Y12 H1/H2haplotype and 10(2.3%)showed P2Y12 H2/H2 haplotyp with a platelet count of(216.09±58.76)×109/L,(195.06±55.16)×109/L and(164.90±46.12)×109/L,respectively(P<0.01).Multivariate logistic regression analysis suggested that platelet count was correlated with P2Y12 H2 haplotype after adjustment of age and gender(P=0.005).Conclusion The effect of P2Y12 H2haplotype on aspirin antiplatelet function is not significant.The number of platelets is significantly lower in patients carrying P2Y12 H2 haplotype than in those carrying P2Y12 H1haplotype,indicating that P2Y12 H2 haplotype is a genetic marker for the lower platelet count in normal populations.