本文選題：氯吡格雷抵抗 + CYP2C19基因多態(tài)性�。� 參考：《昆明醫(yī)科大學(xué)》2016年碩士論文

【摘要】：[目的]研究CYP2C19基因多態(tài)性與患者服用氯吡格雷后達(dá)到穩(wěn)態(tài)血藥濃度時(shí)藥物效果之間的相關(guān)性研究。[方法]選取2015年11月至2016年02月在昆明醫(yī)科大學(xué)第一附屬醫(yī)院心臟內(nèi)科住院的冠心病患者,符合入選標(biāo)準(zhǔn)及排除標(biāo)準(zhǔn)的冠心病患者共72例。首先運(yùn)用PL系列多參數(shù)血小板功能分析儀檢測(cè)患者服用氯吡格雷前血小板最大聚集率(Platelet Maximum Aggregation Rate, MAR)作為基線(xiàn),再給予75mmg氯吡格雷連續(xù)服用5天后,氯吡格雷達(dá)到穩(wěn)態(tài)血藥濃度時(shí),檢測(cè)患者服用氯吡格雷后MAR下降百分比,同時(shí)應(yīng)用DNA微陣列芯片技術(shù)檢測(cè)CYP2C19基因型,并采用液質(zhì)聯(lián)用色譜方法測(cè)定氯吡格雷活性代謝產(chǎn)物濃度。通過(guò)DNA微陣列芯片技術(shù)檢測(cè)研究對(duì)象CYP2C19的基因型,根據(jù)CYP2C19基因型第681號(hào)及第636號(hào)堿基對(duì)等位基因功能缺失分為：快代謝組(野生型*1/*1(681GG/636GG))、中間代謝組(突變雜合型*1/*2 (636GG/681GA)、*1/*3(636GA/681GG))、慢代謝組(突變純合型*2/*2 (636GG/681AA)、*2/*3 (636GA/681GA)、*3/*3 (636AA/681GG)),按上述分組分析：CYP2C19基因型各組之間與氯吡格雷活性代謝產(chǎn)物濃度之間的相關(guān)性。再根據(jù)服用氯吡格雷前后MAR差值,計(jì)算出血小板聚集抑制率(Inhibition rate of Platelet Aggregation, IPA)分為：有效組(IPA≥30%)、中度有效組(IPA15%至30%范圍)、無(wú)效組(IPA15%),按上述分組分析：IPA各組之間與氯吡格雷活性代謝產(chǎn)物濃度之間的相關(guān)性；IPA各組之間與CYP2C19基因型各組之間的相關(guān)性。[結(jié)果]1、CYP2C19基因型,快代謝組的有效率最高為80%,其次為中間代謝的12.50%,慢代謝的0%,差異有統(tǒng)計(jì)學(xué)意義；2、CYP2C19基因型,未變異的有效率為80%,高于變異的8.51%；差異有統(tǒng)計(jì)學(xué)意義；3、氯吡格雷活性代謝產(chǎn)物衍生物濃度,有效組的藥物代謝產(chǎn)物濃度(ng/ml)最高為33.70±4.53,其次中度有效組的為21.18±5.68,無(wú)效組的為10.25±2.47；差異有統(tǒng)計(jì)學(xué)意義；4、活性代謝產(chǎn)物衍生物藥物濃度,快代謝組的藥物代謝產(chǎn)物濃度(ng/ml)最高為33.40±4.52,其次中間代謝組的為21.18±5.56,慢代謝組的為9.91±1.97；差異有統(tǒng)計(jì)學(xué)意義。[結(jié)論]1、根據(jù)血小板聚集抑制率分組的三組中,CYP2C19基因型中的快代謝組在有效組中的比例最高,各組間差異有統(tǒng)計(jì)學(xué)意義,該研究提示快代謝組的療效最好；2、根據(jù)血小板聚集抑制率分組的三組中,CYP2C19基因型中的未變異組在有效組中的比例最高,各組間差異有統(tǒng)計(jì)學(xué)意義,該研究提示未變異組的療效最好；3、根據(jù)血小板聚集抑制率分組的三組中,氯吡格雷活性代謝產(chǎn)物衍生物濃度在有效組中的藥物代謝產(chǎn)物濃度最高,各組間差異有統(tǒng)計(jì)學(xué)意義,該研究提示氯吡格雷療效與氯吡格雷活性代謝產(chǎn)物濃度相關(guān)；4、根據(jù)CYP2C19基因型分出的三種代謝類(lèi)型組,氯吡格雷活性代謝產(chǎn)物衍生物濃度在快代謝組的藥物代謝產(chǎn),物濃度最高,各組間差異有統(tǒng)計(jì)學(xué)意義,該研究提示氯吡格雷活性代謝產(chǎn)物濃度與CYP2C19基因型相關(guān)。
[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，

本文編號(hào)：1954182