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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。
Objective: To evaluate the effect of haplotype of platelet receptor gene P2RY12 mutation on platelet reactivity after clopidogrel in patients with acute coronary syndrome. Innovations: For the first time in China, five common P2RY12 loci including regulatory genes were haploid analyzed and the effect of CYP2C19 gene polymorphism was corrected. It was found that combined mutation of common P2RY12 loci can reduce chlorine The incidence of platelet reactivity after treatment with pioglitazone was more pronounced in non-smokers. Methods: One hundred and eighty consecutive patients with acute coronary syndrome treated with clopidogrel drug were enrolled in this study. Thrombocytopenia was used to detect platelet reactivity in patients. The platelet inhibitory rate was defined as platelet reactivity (HTPR ). Five gene loci (rs6798347, rs6787801, rs6801273, rs6785930 and rs2046934) and three common CYP2C19 alleles (* 2, * 3) covering the P2RY12 regulatory gene were detected by the multiplex ligase detection reaction (LDR) And * 17) for genotyping. According to the linkage disequilibrium coefficient and gene distribution frequency, the haplotype analysis was performed to observe the effects of different P2RY12 haplotypes on the HTPR after clopidogrel administration after the CYP2C19 gene polymorphism was corrected. Conclusion: The four closely linked single nucleotide polymorphisms (SNPs) of rs6798347, rs6787801, rs6801273 and rs6785930 of P2RY12 gene are divided into six common haplotypes (H_0 ~ H_5, Table 4). Haplotype haplotype was significantly associated with the incidence of HTPR after clopidogrel administration, but the incidence of HTP was significantly lower than that of H_0, while rs2046934 had no significant effect on the incidence of HTPR (Table 5) Haplotype haplotype HTPR more obvious impact (Figure 1). In summary, the haplotypes of rs6798347, rs6787801, rs6801273 and rs6785930 of P2RY12 gene were significantly associated with HTPR after clopidogrel treatment.