本文關(guān)鍵詞： 細(xì)胞色素P450 2E1 抗結(jié)核藥 藥物性肝損害 基因多態(tài)性　出處：《山西醫(yī)科大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的很多實(shí)驗(yàn)都致力于研究細(xì)胞色素P450 2E1基因多態(tài)性與抗結(jié)核藥物性肝損害之間的關(guān)系,但是存在爭(zhēng)議。本研究的目的是集發(fā)表過(guò)的關(guān)于細(xì)胞色素P450 2E1基因多態(tài)性與抗結(jié)核藥物性肝損害之間關(guān)系的病例對(duì)照研究,進(jìn)行meta分析。方法利用Medline/Pubmed,EMBASE,ISI Web of Science,CNKI和萬(wàn)方數(shù)據(jù)庫(kù)系統(tǒng)檢索相關(guān)文獻(xiàn),檢索詞包括:藥物代謝酶/drug-metabolising enzymes,抗結(jié)核藥/antitubercular agents,藥物性肝毒性/drug-induced hepatotoxicity,藥物性肝損害/drug-induced liver injury,基因多態(tài)性/genetic polymorphism,細(xì)胞色素酶2E1/cytochrome 2E1,乙�；硇�/acetylator phenotype,基因易感性/genetic susceptibility等。納入2000.1.1到2016.10.31研究細(xì)胞色素P450 2E1基因多態(tài)性與抗結(jié)核藥物性肝損害風(fēng)險(xiǎn)關(guān)系的相關(guān)文獻(xiàn),由2名研究者獨(dú)立進(jìn)行文獻(xiàn)篩選和數(shù)據(jù)提取,并進(jìn)行質(zhì)量評(píng)價(jià)。細(xì)胞色素P450 2E1與抗結(jié)核藥物性肝損害之間關(guān)聯(lián)強(qiáng)度用OR值和95%可信區(qū)間表示。χ~2檢驗(yàn)和I2檢驗(yàn)對(duì)同類(lèi)研究間的異質(zhì)性進(jìn)行評(píng)價(jià)。結(jié)果最終納入符合標(biāo)準(zhǔn)的相關(guān)文獻(xiàn)共21篇,含病例組1114例,對(duì)照組5724例。Meta分析結(jié)果顯示:性別與抗結(jié)核藥物性肝損害風(fēng)險(xiǎn)關(guān)系總OR值為0.95,95%可信區(qū)間:0.72-1.26,P=0.73,種族分層后印度人群OR值為0.74,95%可信區(qū)間:0.56-0.97,P=0.03;細(xì)胞色素P450 2E1 c1/c1基因型與抗結(jié)核藥物性肝損害風(fēng)險(xiǎn)關(guān)系總OR值為1.20,95%可信區(qū)間:1.02-1.41,P=0.03,種族分層后東亞人群OR值為1.34,95%可信區(qū)間:1.11-1.63,P=0.003;細(xì)胞色素P450 2E1 DD基因型與抗結(jié)核藥物性肝損害風(fēng)險(xiǎn)關(guān)系總OR值為0.74,95%可信區(qū)間:0.52-1.05,P=0.09;NAT2慢乙�；硇团c抗結(jié)核藥物性肝損害風(fēng)險(xiǎn)關(guān)系總OR值為2.63,95%可信區(qū)間:2.18-3.18,P0.00001;當(dāng)NAT2慢乙酰化表型與細(xì)胞色素P450 2E1 c1/c1基因型同時(shí)存在時(shí),總OR值為3.61,95%可信區(qū)間:2.18-5.99,P0.00001。結(jié)論Meta分析結(jié)果表明,細(xì)胞色素P450 2E1 c1/c1基因型可能會(huì)增加抗結(jié)核藥物性肝損害的發(fā)生風(fēng)險(xiǎn),尤其在東亞人群中,這種趨勢(shì)更加明顯;NAT2慢乙酰化表型同樣會(huì)增加抗結(jié)核藥物性肝損害的發(fā)生風(fēng)險(xiǎn),并且當(dāng)NAT2慢乙�；硇团c細(xì)胞色素P450 2E1 c1/c1基因型同時(shí)存在時(shí),抗結(jié)核藥物性肝損害的風(fēng)險(xiǎn)將會(huì)明顯增加。
[Abstract]:Objective to study the relationship between cytochrome P450 2E1 gene polymorphism and anti-tuberculosis drug induced liver damage. The aim of this study is to collect published case-control studies on the relationship between cytochrome P450 2E1 gene polymorphisms and antituberculotic liver damage. Methods Medline / Pubmeda Web of Science was used for meta analysis. CNKI and Wanfang database system were used to search the related literatures. The key words were: drug metabolism enzyme / drug metabolism enzymes. Antituberculous drug / drug induced hepatotoxicity. Drug-induced liver injury. genetic polymorphism. Cytochrome 2E1, acetylator phenotype. Genetic susceptibility et al. Study on cytochrome P450 from January 1, 2001 to October 31, 2016. 2the relationship between the polymorphism of E1 gene and the risk of liver injury induced by anti-tuberculosis drugs. Literature screening and data extraction were carried out by two researchers independently. Quality evaluation. Cytochrome P450. 2the intensity of association between E1 and anti-tuberculosis drug induced liver damage was expressed by OR value and 95% confidence interval. 蠂 ~ 2 test and I _ 2 test were used to evaluate the heterogeneity of the same kind of study. There were 21 related articles. There were 1114 cases in the case group and 5724 cases in the control group. The results of meta-analysis showed that the total OR value was 0.95 between sex and the risk of anti-tuberculosis drug induced liver damage. 95% confidence interval: 0.72-1.26: P: 0.73, OR value of Indian population after racial stratification was 0.7495%: 0.56-0.97P0. 03; The total OR value of cytochrome P450 2E1 c1 / c1 genotype and the risk of liver damage induced by anti-tuberculosis drugs was 1.2095% CI: 1.02-1.41P 0.03. After racial stratification, the OR value of East Asian population was 1.34 95% CI: 1.11-1.63P0. 003; The relationship between cytochrome P450 2E1 DD genotype and the risk of liver damage induced by anti-tuberculosis drugs was 0.74% 95% CI: 0.52-1.05P 0.09; The relationship between NAT2 slow acetylation phenotype and the risk of liver injury induced by antituberculous drugs was 2.63% 95% CI: 2.18-3.18% P 0.00001; When the NAT2 slow acetylation phenotype and cytochrome P450 2E1 c1 / c1 genotype existed simultaneously, the total OR value was 3.61% 95% CI: 2.18-5.99. Conclusion Meta analysis shows that cytochrome P450 2E1 c1 / C1 genotype may increase the risk of liver damage induced by anti-tuberculosis drugs. Especially in the East Asian population, this trend is more obvious; The NAT2 slow acetylation phenotype also increases the risk of liver damage induced by antituberculotic drugs. And when the NAT2 slow acetylation phenotype and cytochrome P450 2E1 c1 / c1 genotype co-exist, the risk of liver damage induced by antituberculotic drugs will be significantly increased.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R575

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本文編號(hào)：1493010