Yun-Jian Sheng1, Gang Wu1, Hong-Yan He2, Wen Chen1, Yong-Sheng Zou1, Qin Li1, Li Zhong1, Yong-Mao Huang1, Cun-Liang Deng3. 1. Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China. 2. School of Public Health of LuZhou Medical College, LuZhou 646000, China. 3. Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China. Electronic address: dengcunl7744@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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 CYP2E1PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. RESULTS: 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). CONCLUSION: 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.
Authors: Daniel J Klein; Sotiria Boukouvala; Ellen M McDonagh; Scott R Shuldiner; Nicola Laurieri; Caroline F Thorn; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2016-09 Impact factor: 2.089