CYP2E1 genotype and transaminase level of tuberculosis patients receiving fixed dose combination of antituberculosis

Introductions: Antituberculosis drug-induced liver injury (ATLI) had become a common serious side effect regarding anti-tuberculosis use. Isoniazid (INH) was believed as a significant factor related to ATLI incidence. A genetic factor related to INH metabolism (e.g., CYP2E1) was assumed as a major contributor of ATLI. This study aimed to investigate the genotype pattern of CYP2E1 and serum transaminase level on tuberculosis patients receiving a fixed-dose combination of anti-tuberculosis. Methods: As many as 35 tuberculosis patients attending Pulmonary Outpatient Clinic of Sanglah Hospital were included in this cross-sectional study. Identification of CYP2E1 genotype was performed with a PCR-RFLP assay using RsaI and DraI restriction enzymes. Results: This study revealed the proportion of c1/c1; c1/c2; and c2/c2 genotype of CYP2E1 on 5’-flanking region were 62.9%; 34.3%; and 2.8%, respectively; whereas the proportion of DD, CD and CC genotype of CYP2E1 on intron 6 were 60%; 28.6%; and 11.4%, respectively. The proportion of hepatotoxicity was 14.3%, while the average level of AST and ALT were 23.5±13.6 IU/L and 23.3±21.1 IU/L. There was no significant correlation between CYP2E1 genotypes and hepatotoxicity incidence. Conclusions: The dominant proportion of CYP2E1 genotype on 5’-flanking region and intron 6 are c1/c1 and DD. However, we found no significant differences between CYP2E1 genotypes and hepatotoxicity. Keyword: antituberculosis drug-induced liver injury, isoniazid, CYP2E1 genotype