MDR1,CYP2C19和CYP3A5基因多態(tài)性與氯吡格雷抗凝療效關(guān)系的研究
發(fā)布時(shí)間:2018-06-07 13:35
本文選題:多耐藥基因 + 細(xì)胞色素P450酶2C19。 參考:《河北北方學(xué)院》2014年碩士論文
【摘要】:本研究探討CYP2C19*2,*3,CYP3A5*3,MDR1C3435T基因多態(tài)性對PCI術(shù)后冠狀動脈粥樣硬化性心臟病(冠心。┗颊呗冗粮窭卓鼓熜У南嚓P(guān)性。 選取137例PCI術(shù)后冠心病患者為研究對象,記錄患者性別、年齡、患病史、合并用藥等資料,采用基因芯片法測定CYP2C19*2,*3基因型,直接測序法檢測CYP3A5*3和MDR1C3435T基因型,血栓彈力圖測定患者服用氯吡格雷后體內(nèi)的ADP抑制率。根據(jù)基因型不同進(jìn)行分組,比較不同基因型組患者服用氯吡格雷后產(chǎn)生的ADP抑制率情況差異。 137例確診為冠心病患者納入研究,CYP2C19*1/*1型67例(48.91%),CYP2C19*1/*2型50例(36.50%),CYP2C19*2/*2型8例(5.84%),CYP2C19*1/*3型8例(5.84%),CYP2C19*2/*3型3例(2.19%),CYP2C19*3/*3型1例(0.73%),CYP2C19*2等位基因突變頻率為25.18%,CYP2C19*3等位基因突變頻率為4.74%;MDR13435CC型48例(35.04%),MDR13435CT型68例(49.64%),MDR13435TT型21例(15.33%),MDR13435等位基因突變頻率為40.14%;CYP3A5*1/*1型13例(9.49%),CYP3A5*1/*3型49例(35.77%),CYP3A5*3/*3型75例(54.74%),CYP3A5*3等位基因突變頻率為72.63%。 CYP2C19快代謝(CYP2C19*1/*1)、慢代謝(CYP2C19*1/*2,*1/*3,*2/*2,*2/*3,*3/*3)基因型組患者ADP抑制率分別為(41.99±26.86)%,(33.67±20.53)%,不同CYP2C19基因型組患者ADP抑制率存在顯著性差異(P=0.019)。 MDR13435快代謝(CC)、慢代謝(CT,TT)基因型組患者ADP抑制率分別為(40.25±25.79)%,(36.38±23.19)%,不同MDR13435基因型患者ADP抑制率無顯著性差異(P=0.65)。 CYP3A5快代謝(CYP3A5*1/*1,*1/*3)、慢代謝(CYP3A5*3/*3)基因型組患者ADP抑制率分別為(37.93±24.30)%,(37.57±24.11)%,不同CYP3A5基因型患者ADP抑制率無顯著性差異(P=0.83)。 CYP2C19與MDR1基因聯(lián)合作用對ADP抑制率有統(tǒng)計(jì)學(xué)差異,同時(shí)攜帶CYP2C19慢代謝基因和MDR1慢代謝基因的患者,其ADP抑制率明顯低于CYP2C19基因快代謝型患者(P0.05)。CYP1C19與CYP3A5基因聯(lián)合作用對ADP抑制率并無明顯的統(tǒng)計(jì)學(xué)差異。 PCI術(shù)后冠心病患者,CYP2C19,MDR1基因多態(tài)性影響氯吡格雷的療效,,CYP2C19慢代謝基因型患者,尤其對于CYP2C19和MDR1基因型均為慢代謝基因型的患者,以氯吡格雷作為抗凝劑時(shí)需增加劑量,或改用其他藥物以達(dá)到良好的抗凝效果;PCI術(shù)后冠心病患者,CYP3A5基因多態(tài)性不影響氯吡格雷的療效,了解患者CYP2C19和MDR1基因型,有利于氯吡格雷的個(gè)體化用藥。
[Abstract]:The aim of this study was to investigate the relationship between CYP2C19A5, CYP3A5, MDR1C3435T polymorphism and anticoagulant efficacy of clopidogrel in patients with coronary atherosclerotic heart disease (coronary heart disease) after PCI. 137 patients with coronary heart disease after PCI were selected as the study subjects. The data of sex, age, history of disease and combined use of drugs were recorded. The genotypes of CYP2C19O2O3 were detected by gene chip method, and CYP3A5*3 and MDR1C3435T genotypes were detected by direct sequencing method. Thromboelastography was used to measure the inhibition rate of ADP in patients with clopidogrel. According to different genotypes, the inhibition rate of ADP in different genotype groups was compared after taking clopidogrel. 137渚嬬‘璇婁負(fù)鍐犲績鐥呮?zhèn)h呯撼鍏ョ爺絀
本文編號:1991348
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