血小板二磷酸腺苷受体基因多态性与阿司匹林抵抗关联研究

Association between platelet adenosine diphosphate receptor genetic polymorphism and aspirin resistance

目的分析血小板二磷酸腺苷（ADP）受体P2Y，和P2Y12基因多态性是否对阿司匹林抗血小板作用产生影响。方法入选服用阿司匹林（75～100mg／d，≥1个月）的缺血性心脑血管病患者431例，根据阿司匹林抵抗（AR）诊断标准，分为AR组59例，非AR组372例，并使用美国Sequenom系统单核苷酸多态性分型技术对P2Y，rs1065776（893C〉T）和P2Y12rs5853517（i-ins801A，H1／H2单体型）2个位点进行鉴定和分析。结果AR组血肌酐明显高于非AR组[（92．82±83．07）umol／L vs（78．75±20．41）μmol／L，P=0．01]。2组P2Y1rsl065776突变T等位基因频率分布比较，差异无统计学意义（P〉0．05）。2组携带突变等位基因T的TT＋CT基因型与野生型纯合子CC基因型比较，差异无统计学意义（P〉0．05）。2组P2Y12 H1／H2单体型和突变的H2单体型频率分布比较，差异无统计学意义（P〉0．05）。2组携带突变等住基因H2的H2／H2＋H2／HI基因型与野生型纯合子H1／H1基因型比较，差异无统计学意义（P〉0．05）。结论老年心脑血管病患者AR与血小板ADP受体P2Y1和P2Y12常见的基因多态性无相关性。

Objective To study whether platelet adenosine diphosphate （ADP） receptor P2Y1 and P2YI~ gene polymorphism influences the aspirin resistance （AR） to platelets. Methods Four hun- dred and thirty-one cardio-cerebrovascular disease patients on aspirin therapy （75--100 mg/d,≥l month） were divided into AR group （n=59） and non-AR group （n=372） according to the AR di- agnostic criteria. P2Y1 rs5853517 （893C〉T） and P2Y12 rs5853517 （i-insS01A,H1/H2 haplotype） were identified using the SNP genotyping technique of US Sequenom System. Results The serum creatinine level was significantly higher in AR group than in non-AR group （92. 82 ± 83. 07 μmol/L vs 78.75±20.41 Ixmol/L,P〈0.01）. No significant difference was found in the frequency distribution of mutant T allele in P2Yt rs1065776 （893C〉T）, mutant T allele TT＋CT genotype and wild CC, P2Ylz H1/H2 and mutant H2 haplotype, H2/H2 ＋H2/H1 genotype and wild H1/H1 between the two groups （P〉0.05）. Conclusion AR is not related with platelet ADP receptor P2Y1 and P2YI2 gene polymorphism in elderly Chinese patients with cardio-cerebrovascular disease.