Sheng Yun-Jian, Wu Gang, He Hong-Yan, Chen Wen, Zou Yong-Sheng, Li Qin, Zhong Li, Huang Yong-Mao, Deng Cun-Liang
Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
School of Public Health of LuZhou Medical College, LuZhou 646000, China.
Infect Genet Evol. 2014 Jun;24:34-40. doi: 10.1016/j.meegid.2014.01.034. Epub 2014 Mar 6.
Although there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial.
We searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied.
Compared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI: 1.1-1.82, P=0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI: 0.51-1.18, P=0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (NAT2) fast or intermediate acetylator genotype and c1/c1 genotype patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for ATDH (OR=3.10, P<0.0001).
The present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.
尽管先前已有关于细胞色素P450 2E1（CYP2E1）基因多态性与抗结核药物性肝毒性（ATDH）风险之间潜在关联的研究，但结果普遍存在争议。
我们使用以下关键词在Medline/PubMed、EMBASE、科学网和考克兰图书馆进行检索：细胞色素P450 2E1、CYP2E1、多态性、结核病和TB。研究了通过比值比（OR）及95%置信区间（CI）衡量的CYP2E1 PstI/RsaI和Dral多态性与ATDH风险之间关联的强度。
与野生基因型（c1/c1）相比，PstI/RsaI多态性的ATDH的OR为1.41（95% CI：1.1 - 1.82，P = 0.007），Dral多态性的OR为0.78（95% CI：0.51 - 1.18，P = 0.23）。与N - 乙酰转移酶2（NAT2）快速或中间乙酰化基因型个体相比，NAT2慢乙酰化且携带高活性CYP2E1 c1/c1基因型的患者发生ATDH的风险更高（OR = 3.10，P < 0.0001）。
本荟萃分析表明，CYP2E1 c1/c1基因型可能是ATDH的一个风险因素，而慢乙酰化NAT2基因型的同时存在可能会进一步增加这种风险。
