Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients

Abstract

Context: The risk of antituberculosis (TB) drug‑induced liver injury could be determined by patients’ genotype polymorphism of the xenobiotic‑metabolizing enzymes. To find the meaning of cytochrome P‑4502E1 (CYP2E1) polymorphism in TB patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of isoniazid and rifampicin as well as for the outcome and toxicity development during inpatient TB treatment. Methods: CYP2E1 genotype was detected with the help of polymerase chain reaction and endonuclease analysis. The level of rifampicin, isoniazid, diene conjugates (DC), and catalase activity in the blood was determined spectrophotometrically. We have considered medical records at the beginning and at the end of inpatient treatment. Statistical Analysis Used: Kruskal–Wallis, ANOVA, and Chi‑square tests were used in this study. Results: The concentration of rifampicin 6 h after its intake was 17.6% higher in carriers of slow metabolizer (SM) CYP2E1 genotype than in patients with rapid metabolizer (RM) genotype that proved a participation of hepatic enzyme CYP2E1 in metabolism of rifampicin. According to obtained results in TB patients with RM genotype, the indexes of cytolysis (alanine aminotransferase, aspartate aminotransferase) and bile stasis (gamma‑glutathione transferase) were higher comparatively to SM genotype both before and after inpatient treatment. This correlated with a higher concentration of DC in the blood (+8.6%) and lower plasma catalase activity (−50.0%) in the patients with RM genotype comparatively with the patients with SM genotypes. Conclusion: Polymorphism of CYP2E1 genotype is an important criterion for the development of hepatotoxicity before and during TB treatment while increased rifampicin level has no influence on it.