中国老年心脑血管疾病患者阿司匹林抵抗与环氧化酶-1单体型关联分析

Correlation analysis of aspirin resistance and cycloxygenase-1 haplotype in old Chinese patients with cardio-cerebrovascular diseases

目的:旨在研究老年心脑血管病患者阿司匹林抵抗与阿司匹林作用靶点环氧化酶-1(COX-1)基因单体型的关联性。方法:入选北京地区服用阿司匹林的老年汉族心脑血管疾病患者431例,通过花生四烯酸诱导光比浊法,筛选出阿司匹林抵抗患者59例作为病例组,372例阿司匹林不抵抗者作为对照组,使用美国Sequenom系统SNP分型技术鉴定了COX-1基因6个常见单核苷酸多态性位点(SNP)与阿司匹林抵抗的关联性。6个SNP分别是:rs1888943(8759C/T)、rs1330344(1676A/G)、rs3842787(exon 2,50C/T,p.Pro17Leu)、rs5787(exon 4,323G/A,p.Arg108Gln)、rs5789(exon7,709C/A,p.Leu237Met)和rs5794(exon10,1330G/A,p.Val481Ile)。结果:突变COX-1单体型CGCGCC,在病例组频率为0.48(57/118),对照组频率为0.39(286/742),显著高于对照组(P≤0.05)。结论:中国老年汉族心脑血管疾病患者阿司匹林抵抗与COX-1单体型相关联,突变COX-1单体型CGCGCC显著增加了阿司匹林抵抗的发病风险。

Objective： To investigate whether cyclooxygenase-1 （COX-1）haplotype is associated, with aspirin resistance. Methods： The participants were 431 old Chinese Han patients with cardiovascular and cerebrovascular diseases who took aspirin. The 59 patients with aspirin resistance （AR） by light transmittance aggregation acted as the cases; the 372 aspirin-sensitive patients were the controls. The relationships between APt and 6 single nucleofide polymorphisms （SNPs） in COX-1 gene. rs1888943 （8759C/T）, rs1330344 （1676A/G）, rs3842787 （exon 2, 50C/T, p.Pro17Leu）, rs5787 （exon 4, 323G/A, p. ARgl08Gln）, rs5789 （exon7, 709C/A, p. Leu237Met） and rs5794 （ex- onl0, 1330G/A, p. Va1481Ile） were investigated by the USA Sequenom high-throughput single nucleotide polymorphisms （SNP） genotyping systems. Results： In this ease-control trial, the frequency of mutant CGCC, CC-haplotype in ease was 0.48 （57/118） and in control was 0.39 （286/742）, which was significantly higher than that of the control group （ P ~〈0.05）. Conduslon： COX-1 haplotype is associated with as- pirin resistance in old Chinese Han patients with cardio-cerebrovascular diseases, mutant CGCGCC-haplotype carriers of COX-1 has a signifi- cant significantly increased risk of AR.