R Deng1, T Yang, Y Wang, N Tang. 1. Department of General Toxicology, National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
Abstract
BACKGROUND AND OBJECTIVE: A number of studies have evaluated the association between cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and the risk of anti-tuberculosis drug-induced liver injury (ATDILI). However, the results were inconsistent. We conducted a meta-analysis to clarify the role of this polymorphism in ATDILI. DESIGN: Two authors independently searched the PubMed, Medline, EMBASE and Chinese National Knowledge Infrastructure databases for studies on the association of CYP2E1 RsaI/PstI polymorphism with risk of ATDILI. Summary odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated. RESULTS: The combined results showed that the CYP2E1 c1/c1 genotype was associated with increased ATDILI risk compared to variant genotypes (c1/c2+c2/c2) (OR 1.36, 95%CI 1.09-1.69). When stratifying for study population, statistically significant results were observed in Chinese (OR 1.47, 95%CI 1.12-1.92) and Korean populations (OR 1.85, 95%CI 1.04-3.30). In comparison with CYP2E1 c1/c2 or c2/c2 with rapid/intermediate acetylators, the risk of ATDILI increased from 1.88 (95%CI 1.14-3.09) for CYP2E1 c1/c1 with rapid/intermediate acetylators to 6.44 (95%CI 3.47-11.97) for CYP2E1 c1/c1 with slow acetylators. CONCLUSION: This meta-analysis suggests that CYP2E1 RsaI/PstI polymorphism may affect susceptibility to ATDILI, particularly among Chinese and Korean populations.
BACKGROUND AND OBJECTIVE: A number of studies have evaluated the association between cytochrome P450 2E1 (CYP2E1) RsaI/PstI polymorphism and the risk of anti-tuberculosis drug-induced liver injury (ATDILI). However, the results were inconsistent. We conducted a meta-analysis to clarify the role of this polymorphism in ATDILI. DESIGN: Two authors independently searched the PubMed, Medline, EMBASE and Chinese National Knowledge Infrastructure databases for studies on the association of CYP2E1 RsaI/PstI polymorphism with risk of ATDILI. Summary odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were calculated. RESULTS: The combined results showed that the CYP2E1 c1/c1 genotype was associated with increased ATDILI risk compared to variant genotypes (c1/c2+c2/c2) (OR 1.36, 95%CI 1.09-1.69). When stratifying for study population, statistically significant results were observed in Chinese (OR 1.47, 95%CI 1.12-1.92) and Korean populations (OR 1.85, 95%CI 1.04-3.30). In comparison with CYP2E1 c1/c2 or c2/c2 with rapid/intermediate acetylators, the risk of ATDILI increased from 1.88 (95%CI 1.14-3.09) for CYP2E1 c1/c1 with rapid/intermediate acetylators to 6.44 (95%CI 3.47-11.97) for CYP2E1 c1/c1 with slow acetylators. CONCLUSION: This meta-analysis suggests that CYP2E1 RsaI/PstI polymorphism may affect susceptibility to ATDILI, particularly among Chinese and Korean populations.
Authors: Conor Duncan Tweed; Genevieve Helen Wills; Angela M Crook; Rodney Dawson; Andreas H Diacon; Cheryl E Louw; Timothy D McHugh; Carl Mendel; Sarah Meredith; Lerato Mohapi; Michael E Murphy; Stephen Murray; Sara Murthy; Andrew J Nunn; Patrick P J Phillips; Kasha Singh; M Spigelman; S H Gillespie Journal: BMC Med Date: 2018-03-28 Impact factor: 8.775