上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (3): 301-.doi: 10.3969/j.issn.1674-8115.2012.03.014

• 论著（临床研究） • 上一篇    下一篇

环氧化酶-2启动子区基因单核苷酸多态性与老年人阿司匹林抵抗的关系

王毅盟1, 倪培华2, 杨 蓉1, 吴洁敏2, 吴 方1   

  1. 上海交通大学 医学院附属瑞金医院, 1.老年科, 2.检验系, 上海 200025
  • 出版日期:2012-03-28 发布日期:2012-03-28
  • 通讯作者: 吴 方, 电子信箱: sjxdmm@tom.com。
  • 作者简介:王毅盟（1984—）, 女, 硕士生；电子信箱: wangyimeng118@163.com。
  • 基金资助:

    上海市教委基金（11YZ57）

Relationship between single nucleotide polymorphisms in promoter region of cyclooxygenase-2 gene and aspirin resistance in the elderly

WANG Yi-meng1, NI Pei-hua2, YANG Rong1, WU Jie-min2, WU Fang1   

  1. 1.Department of Geriatrics, 2.Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2012-03-28 Published:2012-03-28
  • Supported by:

    Shanghai Education Committee Foundation, 11YZ57

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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。

关键词: 环氧化酶-2, 阿司匹林抵抗, 单核苷酸多态性, 单倍型

Abstract:

Objective To explore the relationship between 765G>C, 1195G>A and 1290A>G 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 765G>C, 1195G>A and 1290A>G 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 -765G>C 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 -1195G>A 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 -1290A>G 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 -765G>C, -1195G>A and -1290A>G in non-aspirin sensitive group was significantly higher than that in aspirin sensitive group (P<0.05). Conclusion Haplotype C-G-G of -765G>C, -1195G>A and -1290A>G may be related to aspirin resistance, and -765G>C gene polymorphisms may be genetic risk factor of aspirin resistance for elder patients.

Key words: cyclooxygenase-2, aspirin resistance, single nucleotide polymorphism, haplotype