阿司匹林抵抗与COX-1基因C50T单核苷酸多态性临床研究

The clinical study in both aspirin resistance and cyclooxygenase-1 C50T single nucleotide polymorphism

目的探讨脑梗死患者二级预防中阿司匹林抵抗(aspirin resistance,AR)现象及其与环氧化酶-1(cyclooxygenase-1,COX-1)基因C50T单核苷酸多态性(single nucleotide polymorphism,SNP)的相关性。方法选取入住我科的急性脑梗死患者126例、同期住院的有卒中高危因素的非脑卒中患者80例及健康志愿者30例,分别以花生四烯酸(arachidonic acid,AA)和二磷酸腺苷(adenosine diphosphate,ADP)作为诱导剂,采用比浊法测定血小板聚集率;3组均以多聚酶链式反应结合限制性内切酶片段长度多态分析方法,检测COX-1基因C50T单核苷酸多态性。结果 126例脑梗死患者中有39例存在阿司匹林抵抗(约28%),13例存在阿司匹林半抵抗(约9%),74例对阿司匹林敏感(约63%)。非脑梗死组及健康对照组未发现阿司匹林抵抗现象的存在。且阿司匹林抵抗和半抵抗患者中,高龄、女性、糖尿病、高血脂患者发生率高,均较阿司匹林敏感组有明显的统计学差异(P<0.05);3组患者的COX-1基因C50T单核苷酸多态性的基因型均为纯合体CC,未见基因突变类型。结论高龄女性、糖尿病、高血脂是阿司匹林抵抗的高危因素;国人COX-1基因C50T单核苷酸多态性尚属罕见,其与阿司匹林抵抗的发生无明显相关。

Objective To investigate the phenomenon of aspirin resistance in patients with cerebral infarction during the second prevetion and the relationship with cyclooxygenase-1 C50T single nucleotide polymorphism.Methods 126 patients with acute cerebral infarction,80 patients with stroke risk factors but not infarction during hospitalization and 30 volunteers were prospectively enrolled.The level of platelet aggregation was detected using ADP and AA respectively by turbidimetry.At the same time the C50T single nucleotide polymorphism of COX-1 gene was detected in three groups by polymerase chain reaction with restriction endonuclease fragment length polymorphism.Results 39 out of 126 patients were of aspirin resistance（about 28%）,13 were aspirin semi-resistant（about 9%） and only 74 were aspirin sensitive（about 63%）.At the same time there was no sign of aspirin resistance in both non-cerebral infarction group and healthy control group.Besides,the older women had a high rate with diabetes and hyperlipidemia,which was more obvious in aspirin resistant and semi-resistant groups than aspirin sensitive group.The difference was significant（P 0.05）.The C50T SNP genotype of COX-1 gene in three groups was homozygous CC without types of gene mutation.Conclusion Elderly women,diabetes and hyperlipidemia are high risk factors of aspirin resistance.The C50T single nucleotide polymorphism of COX-1 gene is rare in Chinese population which is not obviously associated with aspirin resistance.