| ObjectiveA number of studies have evaluated the association between CYP450 2E1 polymorphism and anti-tuberculosis drug-induced liver injury.However,the results were inconsistent.We conducted a meta-analysis to clarify the association.MethodsMedline,Pubmed,EMBASE,ISI Web of Science,CNKI and Wan Fang database were searched to identify relevant studies including the words: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,遗传易感性/genetic susceptibility.The time for retrieving was from January 1,2000 to October 31,2016,literatures on association between CYP2E1 polymorphisms and anti-tuberculosis drug-induced liver injury were retrieved,and data was analyzed and evaluated by 2independent researchers.Odds ratios(OR)and 95%confidence intervals(95%CI)were calculated.The heterogeneity was analyzed byχ~2test and I2test.ResultsTwenty-one literatures involving a total of 1114 cases and 5724 controls were finally enrolled in this study.The results of Meta analysis showed: Compared with the gender,the summary OR of ATLI was 0.95(95%CI:0.72-1.26).When studies were stratified for ethnicity,significant risks were found among Indian(OR=0.74,95%CI:0.56-0.97).Compared with the wild genotype(c1/c1),the summary OR of ATLI was 1.20(95%CI:1.02-1.41)for the PstI/RsaI polymorphism.When studies were stratified for ethnicity,significant risks were found among East Asians(OR=1.34,95%CI:1.11-1.63).Compared with the genotype DD,the summary OR of ATLI was 0.74(95%CI:0.52-1.05)for the DraⅠ polymorphism.The summary OR of the NAT2 slow acetylator genotype for ATLI was 2.63(95%CI:2.18-3.18).The summary OR of the NAT2 slow acetylator combine with CYP2E1 c1/c1 genotype for ATLI was 3.61(95%CI:2.18-5.99).ConclusionThe present meta-analysis indicates that CYP450 2E1 c1/c1 genotype may increase the risk of ATLI,especially in East Asian,this trend is more obvious;NAT2 slow acetylation phenotype will also increase the risk of ATLI,and when the NAT2 slow acetylator phenotype combining with CYP450 2E1 genotype c1/c1,the risk of ATLI will increase significantly. |
