细胞色素P450 2E1基因多态性与抗结核药物性肝损伤关系的meta分析

发布时间：2018-02-05 23:14

本文关键词： 细胞色素P450 2E1 抗结核药药物性肝损害基因多态性　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的很多实验都致力于研究细胞色素P450 2E1基因多态性与抗结核药物性肝损害之间的关系,但是存在争议。本研究的目的是集发表过的关于细胞色素P450 2E1基因多态性与抗结核药物性肝损害之间关系的病例对照研究,进行meta分析。方法利用Medline/Pubmed,EMBASE,ISI Web of Science,CNKI和万方数据库系统检索相关文献,检索词包括:药物代谢酶/drug-metabolising enzymes,抗结核药/antitubercular agents,药物性肝毒性/drug-induced hepatotoxicity,药物性肝损害/drug-induced liver injury,基因多态性/genetic polymorphism,细胞色素酶2E1/cytochrome 2E1,乙酰化表型/acetylator phenotype,基因易感性/genetic susceptibility等。纳入2000.1.1到2016.10.31研究细胞色素P450 2E1基因多态性与抗结核药物性肝损害风险关系的相关文献,由2名研究者独立进行文献筛选和数据提取,并进行质量评价。细胞色素P450 2E1与抗结核药物性肝损害之间关联强度用OR值和95%可信区间表示。χ~2检验和I2检验对同类研究间的异质性进行评价。结果最终纳入符合标准的相关文献共21篇,含病例组1114例,对照组5724例。Meta分析结果显示:性别与抗结核药物性肝损害风险关系总OR值为0.95,95%可信区间:0.72-1.26,P=0.73,种族分层后印度人群OR值为0.74,95%可信区间:0.56-0.97,P=0.03;细胞色素P450 2E1 c1/c1基因型与抗结核药物性肝损害风险关系总OR值为1.20,95%可信区间:1.02-1.41,P=0.03,种族分层后东亚人群OR值为1.34,95%可信区间:1.11-1.63,P=0.003;细胞色素P450 2E1 DD基因型与抗结核药物性肝损害风险关系总OR值为0.74,95%可信区间:0.52-1.05,P=0.09;NAT2慢乙酰化表型与抗结核药物性肝损害风险关系总OR值为2.63,95%可信区间:2.18-3.18,P0.00001;当NAT2慢乙酰化表型与细胞色素P450 2E1 c1/c1基因型同时存在时,总OR值为3.61,95%可信区间:2.18-5.99,P0.00001。结论Meta分析结果表明,细胞色素P450 2E1 c1/c1基因型可能会增加抗结核药物性肝损害的发生风险,尤其在东亚人群中,这种趋势更加明显;NAT2慢乙酰化表型同样会增加抗结核药物性肝损害的发生风险,并且当NAT2慢乙酰化表型与细胞色素P450 2E1 c1/c1基因型同时存在时,抗结核药物性肝损害的风险将会明显增加。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

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