摘要
目的研究环氧化酶-2(COX-2)基因启动子765G>C、1195G>A和1290A>G的单核苷酸多态性(SNP)与老年人发生阿司匹林抵抗的关系。方法以162例服用阿司匹林进行抗血栓治疗的老年患者为研究对象,行血小板聚集检测,根据检测结果分组并分析阿司匹林抵抗发生的危险因素。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对COX-2基因启动子765G>C、1195G>A和1290A>G的单核苷酸多态性进行分析。结果根据血小板聚集检测结果,阿司匹林敏感组108例,非阿司匹林敏感组54例。多元逐步Logistic回归分析显示高血压为阿司匹林抵抗发生的独立危险因素。两组间-765G>C SNP位点基因型及等位基因频率分布的差异有统计学意义(P=0.027和P=0.030);Logistic回归分析显示:与-765GG纯合基因携带者相比,-765GC杂合基因携带者对阿司匹林药效不敏感的OR值为3.872(95%CI 1.081～13.870,P=0.038)。两组间-1195G>A SNP位点基因型分布差异有统计学意义(P=0.018),其A、G等位基因频率的差异无统计学意义(P=0.156)。两组间-1290A>G SNP位点基因型分布差异无统计学意义(P=0.091),其A、G等位基因频率分布差异有统计学意义(P=0.025)。阿司匹林非敏感组等位基因-765G>C、-1195G>A和-1290A>G呈单倍型C-G-G的出现频率明显高于阿司匹林敏感组(P<0.05)。结论 -765G>C、-1195G>A和-1290A>G呈单倍型C-G-G与阿司匹林抵抗的发生可能有一定关系,-765G>C基因多态性可能是老年患者发生阿司匹林抵抗的遗传性危险因素。
Objective To explore the relationship between 765GC,1195GA and 1290AG single nucleotide polymorphisms（SNP） in the promoter region of cyclooxygenase-2（COX-2） gene and aspirin resistance in the elderly.Methods One hundred and sixty-two elder patients taking aspirin for antithrombotic therapy were selected,platelet aggregation tests were performed,groups were divided according to test findings,and risk factors of aspirin resistance were analysed.Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） was employed to analyse 765GC,1195GA and 1290AG SNP in the promoter region of COX-2 gene.Results Patients were divided into aspirin sensitive group（n=108） and non-aspirin sensitive group（n=54）.Multiple stepwise Logistic regression analysis indicated that hypertension was an independent risk factor of aspirin resistance.There were significant differences in the genotype distribution and allele frequency of-765GC SNP between two groups（P=0.027,P=0.030）.Logistic regression analysis demonstrated that compared with-765GG genotype,OR of aspirin resistance for-765GC genotype was 3.872（95% CI 1.081-13.870,P=0.038）.There were significant differences in genotype distribution of-1195GA SNP between two groups（P=0.018）,and there was no significant difference in allele frequencies of A and G between them（P=0.156）.There was no significant difference in genotype distribution of-1290AG SNP between two groups（P=0.091）,and there were significant differences in allele frequencies of A and G between them（P=0.025）.The frequency of haplotype C-G-G of-765GC,-1195GA and-1290AG in non-aspirin sensitive group was significantly higher than that in aspirin sensitive group（P0.05）.Conclusion Haplotype C-G-G of-765GC,-1195GA and-1290AG may be related to aspirin resistance,and-765GC gene polymorphisms may be genetic risk factor of aspirin resistance for elder patients.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2012年第3期301-306,共6页
Journal of Shanghai Jiao tong University:Medical Science
基金
上海市教委基金(11YZ57)~~
