<I>CYP2E1 RsaI/PstI</I> polymorphism and risk of anti-tuberculosis drug-induced liver injury: a meta-analysis [Review article

Abstract

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. 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. 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. This meta-analysis suggests that CYP2E1 RsaI/PstI polymorphism may affect susceptibility to ATDILI, particularly among Chinese and Korean populations.