急性冠脉综合征抗血小板治疗药物抵抗及与COX-1基因多态性的相关性

目的:研究急性冠脉综合征(ACS)患者对阿司匹林联合氯吡格雷双重抗血小板治疗的反应并探讨药物抵抗与血小板COX-1基因A842G位点的相关性。方法:154例ACS患者,以花生四烯酸(AA)作为诱导剂测定血小板聚集率(PAG)。ELISA法测定尿11-脱氢-血栓素B2(11-DH-TXB2)水平。分析血小板COX-1基因A842G位点的基因型。计算患者2周内主要临床心脏事件(MACE)发生率。结果:①154例ACS患者PAG及尿11-DH-TXB2水平均明显升高,且急性心肿梗死(AMI)患者高于不稳定性心绞痛(UAP)患者,组间比较存在统计学差异(t=2.994,P<0.01;t=2.053,P<0.01);②双重抗血小板药物抵抗(AR)6例,抵抗发生率为3.90%;③COX-1基因A842G位点基因型AA型150例(97.40%),AG型4例(2.60%)。AR患者6例,其中AA型患者5例(83.33%),AG型患者1例(16.67%),组间比较存在统计学差异(χ2=43.560,P<0.01);④2周内AR组MACE率33.33%(2例),AS组4.05%(6例),组间比较存在统计学差异(χ2=22.73,P<0.01)。结论:①ACS患者存在不同程度的血小板活化状态,且AMI患者高于UAP患者,高血小板活化状态能引起更为严重的急性心脏事件;②COX-1基因A842G位点单核苷酸多态性可能与AR的发生有关,含有G突变基因患者更易发生AR;③AR患者更易发生心脏临床事件。

Resistance of Acute Coronary Syndrome Patients to Antiplatelet Drugs and Its Correlation to COX-1 Gene

Objective: To investigate the responses of aspirin plus clopidogrel therapy in patients with acute coronary syndrome(ACS),and to explore the molecular biological mechanism.Methods: A total of 154 patients with ACS received dual antiplatelet drugs treatment as aspirin 100 mg/d and clopidogrel 75 mg/d.Platelet aggregation(PAG) percentage induced by arachidonic acid(AA 0.5 mmol/L) and urinary 11-dehydro-Thromboxane B2(11-DH-TXB2) was tested by ELISA method.The COX-1 gene A842G single nucleotide polymorphism was examined by PCR.Main adverse cardiac events(MACE) rates in two weeks were calculated.Results: ①Of the 154 patients with ACS,113 were acute myocardial infarction(AMI) and 41 were unstable angina pectoris(UAP),and there were significant differences in PAG induced by AA and urinary 11-DH-TXB2 before the dual antiplatelet therapy between the two groups(both P<0.01);②Between the antiplatelet drugs resistance(AR) group(6 patients,3.90%) and sensitive group(AS group,148 patients,96.10%),there were significant differences in PAG induced by AA and urinary 11-DH-TXB2 after the dual antiplatelet therapy(both P<0.01);③In the genotype of the COX-1 gene A842G,150 patients are AA type and 4 patients are AG type,5 of the AR group are AA type(83.33%) and one of them is AG type(16.67%),and there was a significant difference(P<0.01);④The prevalence of MACE in two weeks was 33.33%(2 patients) in AR group and 4.05%(6 patients) in AS group,and there was a significant difference(P<0.01).Conclusion: ①There are some extent of platelet activation in patients with ACS,presented with PAG induced by AA and the high levels of urinary 11-DH-TXB2.②There was a relationship between COX-1 gene A842G single nucleotide polymorphism and antiplatelet resistance,and the patients with mutant gene G are susceptive to AR.③The patients with AR have a higher cardiovascular event rate.