P2RY12基因单倍体分型对急性冠脉综合征患者氯吡格雷用药后血小板反应性的影响（英文）

发布时间：2018-05-25 06:53

本文选题：PRY + CYPC　；参考：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2017年01期

【摘要】：目的:评估血小板受体基因P2RY12常见突变位点单倍体分型对急性冠脉综合征患者氯吡格雷用药后血小板反应性的影响。创新点:首次在中国人群中对包含调控基因在内的五个常见P2RY12突变位点进行单倍体分析,并且校正了CYP2C19基因多态性的影响,发现P2RY12常见基因位点联合突变可降低氯吡格雷用药后血小板高反应性发生率,且作用在不吸烟人群中更明显。方法:连续入选180例接受氯吡格雷药物治疗的急性冠脉综合征患者,利用血栓弹力图法检测患者用药后血小板反应性,将用药后血小板抑制率30%定义为血小板高反应性(HTPR)。用多重连接酶检测反应(LDR)技术,对覆盖P2RY12调控基因在内的五个基因位点(rs6798347、rs6787801、rs6801273、rs6785930和rs2046934)以及CYP2C19常见的三个等位基因(*2、*3和*17)进行基因分型。根据连锁不平衡系数和基因分布频率进行单倍体分析,观察在校正CYP2C19基因多态性影响后,不同P2RY12单倍体分型对氯吡格雷用药后HTPR的影响。结论:将P2RY12基因rs6798347、rs6787801、rs6801273和rs6785930四个紧密连锁的单核苷酸多态性(SNP)分为六个常见单倍体分析(H_0~H_5,表4)。单倍体分型与氯吡格雷用药后HTPR发生率显著相关,与H_0型相比,H_1型HTPR发生率显著降低,而rs2046934对HTPR发生率无显著影响(表5),且在不吸烟组中单倍体分型对HTPR影响更明显(图1)。综上所述,P2RY12基因rs6798347、rs6787801、rs6801273和rs6785930单倍体分型与氯吡格雷用药后HTPR显著相关。
[Abstract]:Aim: to evaluate the effect of haploid typing on platelet reactivity after clopidogrel administration in patients with acute coronary syndrome (ACS). Innovation: for the first time, haploid analysis of five common P2RY12 mutation sites, including regulatory genes, was carried out in Chinese population, and the effect of CYP2C19 gene polymorphism was corrected. It was found that the co-mutation of common gene loci of P2RY12 could reduce the incidence of platelet hyperresponsiveness after clopidogrel administration, and the effect was more obvious in non-smoking population. Methods: 180 consecutive patients with acute coronary syndrome treated with clopidogrel were enrolled. Thromboelastography was used to detect the platelet reactivity after treatment. The platelet inhibition rate (30%) was defined as hyperreactivity of platelet (HTPRN). Five loci, rs6798347, rs6787801, rs6801273, rs6785930 and rs2046934, and the three common alleles of CYP2C19 were genotyped by multiple ligase assay. Haploid analysis was carried out according to linkage disequilibrium coefficient and gene distribution frequency. After adjusting for the effect of CYP2C19 gene polymorphism, the effect of different P2RY12 haploid typing on HTPR after clopidogrel treatment was observed. Conclusion: four closely linked single nucleotide polymorphisms, rs6798347, rs6787801, rs6801273 and rs6785930, were divided into six common haploid analysis, H0H5 and table 4. The haploid type was significantly correlated with the incidence of HTPR after clopidogrel administration, and the incidence of HTPR of type H1 was significantly lower than that of type HSPO, but rs2046934 had no significant effect on the incidence of HTPR (Table 5), and haploid typing had a more significant effect on HTPR in the non-smoking group (Fig. 1). In conclusion, pP2RY12 gene rs6798347rs6787801rs6801273 and rs6785930 haplotypes were significantly correlated with HTPR after clopidogrel administration.
【作者单位】： School
【基金】：Project supported by the Beijing Higher Education Young Elite Teacher Project(No.YETP0064),China
【分类号】：R541.4

【相似文献】