發(fā)布時(shí)間：2018-05-25 06:53

  本文選題：PRY + CYPC�。� 參考：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2017年01期

【摘要】：目的:評(píng)估血小板受體基因P2RY12常見突變位點(diǎn)單倍體分型對(duì)急性冠脈綜合征患者氯吡格雷用藥后血小板反應(yīng)性的影響。創(chuàng)新點(diǎn):首次在中國人群中對(duì)包含調(diào)控基因在內(nèi)的五個(gè)常見P2RY12突變位點(diǎn)進(jìn)行單倍體分析,并且校正了CYP2C19基因多態(tài)性的影響,發(fā)現(xiàn)P2RY12常見基因位點(diǎn)聯(lián)合突變可降低氯吡格雷用藥后血小板高反應(yīng)性發(fā)生率,且作用在不吸煙人群中更明顯。方法:連續(xù)入選180例接受氯吡格雷藥物治療的急性冠脈綜合征患者,利用血栓彈力圖法檢測患者用藥后血小板反應(yīng)性,將用藥后血小板抑制率30%定義為血小板高反應(yīng)性(HTPR)。用多重連接酶檢測反應(yīng)(LDR)技術(shù),對(duì)覆蓋P2RY12調(diào)控基因在內(nèi)的五個(gè)基因位點(diǎn)(rs6798347、rs6787801、rs6801273、rs6785930和rs2046934)以及CYP2C19常見的三個(gè)等位基因(*2、*3和*17)進(jìn)行基因分型。根據(jù)連鎖不平衡系數(shù)和基因分布頻率進(jìn)行單倍體分析,觀察在校正CYP2C19基因多態(tài)性影響后,不同P2RY12單倍體分型對(duì)氯吡格雷用藥后HTPR的影響。結(jié)論:將P2RY12基因rs6798347、rs6787801、rs6801273和rs6785930四個(gè)緊密連鎖的單核苷酸多態(tài)性(SNP)分為六個(gè)常見單倍體分析(H_0~H_5,表4)。單倍體分型與氯吡格雷用藥后HTPR發(fā)生率顯著相關(guān),與H_0型相比,H_1型HTPR發(fā)生率顯著降低,而rs2046934對(duì)HTPR發(fā)生率無顯著影響(表5),且在不吸煙組中單倍體分型對(duì)HTPR影響更明顯(圖1)。綜上所述,P2RY12基因rs6798347、rs6787801、rs6801273和rs6785930單倍體分型與氯吡格雷用藥后HTPR顯著相關(guān)。
[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.
【作者單位】： School
【基金】：Project supported by the Beijing Higher Education Young Elite Teacher Project(No.YETP0064),China
【分類號(hào)】：R541.4

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本文編號(hào)：1932508