BACKGROUND

Anti-tuberculosis drug-induced hepatotoxicity can result from genetic polymorphism of the isoniazid (INH) metabolizing enzyme. This study aimed to determine the effect of genetic polymorphism of N-acetyltransferase 2 () and cytochrome P450 2E1 () genes on serum isoniazid level and drug-induced hepatotoxicity.

METHODS

A cross-sectional study was conducted on 120 patients (with and without hepatotoxicity) with pulmonary tuberculosis from June 2019 to April 2022 in Tehran (Iran). High-performance liquid chromatography was used to measure the serum concentration of INH and acetylisoniazid (AcINH). and genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism methods. Data were analyzed using SPSS software (version 22.0) with independent two-sample test, Chi square test, or Fisher's exac test. P<0.05 was considered statistically significant.

RESULTS

A total of 40 patients showed hepatotoxicity. The risk of anti-tuberculosis drug-induced hepatotoxicity was significantly higher in patients who are slow acetylator (SA) phenotype than in rapid or intermediate acetylator (P<0.001). *4/*4 genotypes were not found in patients with hepatotoxicity. The frequency of *5 and *6 haplotypes and serum INH concentration was significantly higher in patients with hepatotoxicity than in those without (P=0.003, P<0.001, and P<0.001, respectively). *4 haplotype was correlated with protection against hepatotoxicity. A combination of SA and C1/C1 genotype was significantly associated with hepatotoxicity (P<0.001).

CONCLUSION

Hepatotoxicity in Iranian patients with tuberculosis was confirmed due to the presence of SA polymorphism. Determining and genotypes and/or INH concentration can be a valuable tool to identify patients susceptible to hepatotoxicity.