CYP2C19基因多态性与稳态血药浓度对氯吡格雷抵抗的相关性研究

发布时间：2018-05-30 05:57

  本文选题：氯吡格雷抵抗 + CYP2C19基因多态性　； 参考：《昆明医科大学》2016年硕士论文

【摘要】：[目的]研究CYP2C19基因多态性与患者服用氯吡格雷后达到稳态血药浓度时药物效果之间的相关性研究。[方法]选取2015年11月至2016年02月在昆明医科大学第一附属医院心脏内科住院的冠心病患者,符合入选标准及排除标准的冠心病患者共72例。首先运用PL系列多参数血小板功能分析仪检测患者服用氯吡格雷前血小板最大聚集率(Platelet Maximum Aggregation Rate, MAR)作为基线,再给予75mmg氯吡格雷连续服用5天后,氯吡格雷达到稳态血药浓度时,检测患者服用氯吡格雷后MAR下降百分比,同时应用DNA微阵列芯片技术检测CYP2C19基因型,并采用液质联用色谱方法测定氯吡格雷活性代谢产物浓度。通过DNA微阵列芯片技术检测研究对象CYP2C19的基因型,根据CYP2C19基因型第681号及第636号碱基对等位基因功能缺失分为：快代谢组(野生型*1/*1(681GG/636GG))、中间代谢组(突变杂合型*1/*2 (636GG/681GA)、*1/*3(636GA/681GG))、慢代谢组(突变纯合型*2/*2 (636GG/681AA)、*2/*3 (636GA/681GA)、*3/*3 (636AA/681GG)),按上述分组分析：CYP2C19基因型各组之间与氯吡格雷活性代谢产物浓度之间的相关性。再根据服用氯吡格雷前后MAR差值,计算出血小板聚集抑制率(Inhibition rate of Platelet Aggregation, IPA)分为：有效组(IPA≥30%)、中度有效组(IPA15%至30%范围)、无效组(IPA15%),按上述分组分析：IPA各组之间与氯吡格雷活性代谢产物浓度之间的相关性；IPA各组之间与CYP2C19基因型各组之间的相关性。[结果]1、CYP2C19基因型,快代谢组的有效率最高为80%,其次为中间代谢的12.50%,慢代谢的0%,差异有统计学意义；2、CYP2C19基因型,未变异的有效率为80%,高于变异的8.51%；差异有统计学意义；3、氯吡格雷活性代谢产物衍生物浓度,有效组的药物代谢产物浓度(ng/ml)最高为33.70±4.53,其次中度有效组的为21.18±5.68,无效组的为10.25±2.47；差异有统计学意义；4、活性代谢产物衍生物药物浓度,快代谢组的药物代谢产物浓度(ng/ml)最高为33.40±4.52,其次中间代谢组的为21.18±5.56,慢代谢组的为9.91±1.97；差异有统计学意义。[结论]1、根据血小板聚集抑制率分组的三组中,CYP2C19基因型中的快代谢组在有效组中的比例最高,各组间差异有统计学意义,该研究提示快代谢组的疗效最好；2、根据血小板聚集抑制率分组的三组中,CYP2C19基因型中的未变异组在有效组中的比例最高,各组间差异有统计学意义,该研究提示未变异组的疗效最好；3、根据血小板聚集抑制率分组的三组中,氯吡格雷活性代谢产物衍生物浓度在有效组中的药物代谢产物浓度最高,各组间差异有统计学意义,该研究提示氯吡格雷疗效与氯吡格雷活性代谢产物浓度相关；4、根据CYP2C19基因型分出的三种代谢类型组,氯吡格雷活性代谢产物衍生物浓度在快代谢组的药物代谢产,物浓度最高,各组间差异有统计学意义,该研究提示氯吡格雷活性代谢产物浓度与CYP2C19基因型相关。
[Abstract]:[objective] to study the correlation between CYP2C19 gene polymorphism and drug efficacy when clopidogrel was given clopidogrel. [methods] from November 2015 to February 2016, 72 patients with coronary heart disease (CHD) who were admitted to the Department of Cardiology, first affiliated Hospital of Kunming Medical University, met the criteria of inclusion and exclusion. The maximum platelet aggregation rate before taking clopidogrel and Platelet Maximum Aggregation Rate, MAR) were measured by PL series multiparameter platelet function analyzer as baseline. After 75mmg was administered continuously for 5 days, clopidogrel reached steady blood concentration. The percentage of MAR decreased after administration of clopidogrel, the CYP2C19 genotype was detected by DNA microarray technique, and the concentration of active metabolites of clopidogrel was determined by HPLC. The genotypes of CYP2C19 were detected by DNA microarray technology. According to the functional deletions of the 681 and 636 base pairs of CYP2C19 genotypes, they were divided into: fast metabolic group (wild type 1 / 1 / 1 681G / 636G / 636G), intermediate metabolic group (mutant heterozygous 1 / 2 / 636G / 681GA / 636G / 681GG), slow metabolic group (636G / 636G / 681G / 636G / 636G / 6681GG / 636A / 6681GG / 636A / 6681GG / 636A / 6681G / 636A / 6681GG / 636A / 636A / 6681G / 636A / 6681G / 636A / 6681G / 636A / 6681G / 636A / 6681G / 636A / P 636A / 6681G / 636A / 6681G / 636A / 6681@@ Correlation between CYP2C19 genotypes and clopidogrel active metabolite concentrations. Then according to the difference of MAR before and after taking clopidogrel, The inhibition rate of platelet aggregation was calculated and the inhibition rate of Platelet Aggregation, IPA) was divided into three groups: the effective group was IPA鈮，

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