环氧化酶1与2基因多态性与缺血性脑卒中患者阿司匹林抵抗的相关性研究

Association between cyclooxygenase-1/-2 genetic polymorphisms and aspirin resistance in ischemic stroke patients

目的 考察环氧化酶1与2（COX-1、COX-2）的基因多态性与阿司匹林抵抗的相关性研究.方法纳入192例中国缺血性脑卒中患者,持续服用阿司匹林100 mg,收集全血提取DNA,进行COX-1（1676G〉A,rs1330344）、（128G〉A,rs3842788）、（644C〉A,rs5788）及COX-2（765G〉C,rs20417）4个单核苷酸多态性（SNPs）的基因型分析,用花生四烯酸（AA）和二磷酸腺苷（ADP）诱导光比浊法测定血小板聚集功能;并分析其相关性.结果 患者分为阿司匹林敏感组与非敏感组,COX-1（rs1330344）及COX-1（rs3842788）基因型分布在2组间差异有统计学意义（均P〈0.05）,COX-1（rs3842788）GG型为阿司匹林抵抗发生的危险因素（OR=10.750,95% CI：1.418~81.509）.COX-1（rs5788）及COX-2（rs20417）基因型分布在2组间差异无统计学意义（P〉0.05）.结论 在中国缺血性脑卒中患者中,COX-1（rs3842788）GG型与阿司匹林抵抗的发生密切相关.

Objective To investigate the correlation between cyclooxygenase 1 and 2（COX-1 and COX-2） genetic polymorphisms and the resistances after treatment with aspirin. Methods One hundred and ninety-two Chinese ischemic stroke patients who continue to take aspirin （100 mg daily） were prospectively enrolled. And the DNA was extracted from whole boold, then genotype analysis of four SNPs among COX-1（1676G〉A,rs1330344）, （128G〉A,rs3842788）, （644C〉A,rs5788）and COX-2（765G〉C,rs20417） was made. Their correlations with arachidonic acid （AA） and adenosine diphosphate （ADP） induced optical turbidimetric method platelet aggregation function were analyzed. The correlations were evaluated by Chi-square test or Fisher′s exact test. Results Both COX-1 genetic polymorphisms rs1330344 and rs3842788 genotype frequencies were significantly different between aspirin sensitive and non-sensitive groups （both P〈0.05）. Especially, COX-1 （rs3842788） GG genotype was correlated with an increased risk of AR （OR=10.750, 95% CI： 1.418-81.509）. However, no differences in the genotype frequencies of the COX-1 rs5788 and COX-2 rs20417genetic polymorphisms were detected between the aspirin sensitive and non-sensitive groups （P〉0.05）. Conclusion Among Chinese patients with ischemic stroke, COX - 1 （rs3842788） GG type is closely related to the occurrence of aspirin resistance.