Study of the Effect of Polymorphic Markers of the NAT2 Gene on the Risk of Adverse Drug Reactions in Patients with Pulmonary Tuberculosis Who Received Isoniazid and Rifampicin

Abstract

Tuberculosis remains one of the most dangerous and widespread infectious diseases. More than 20 medicinal products are currently available for the treatment of tuberculosis. One of the most serious adverse drug reactions (ADRs) associated with anti-tuberculosis medicines is hepatotoxicity.The aim of the study was to assess the effect of polymorphic markers of the NAT2 gene on the ADR risk in patients with pulmonary tuberculosis who received isoniazid and rifampicin.Materials and methods. The study included 67 patients with different forms of pulmonary tuberculosis who received combination therapy with isoniazid and rifampicin. Single nucleotide polymorphisms (SNPs) of the NAT2 gene were determined by real-time PCR. Statistical processing was performed using SPSS Statistics 20.0.Results: Six SNPs were identified in the NAT2 gene. Based on these SNPs the following phenotypes were determined by the rate of NAT2 acetylation: fast acetylators—6 subjects, intermediate acetylators—24 subjects, and slow acetylators—37 subjects. The study assessed the relationship between the acetylator phenotype and the development of ADRs during combination therapy with isoniazid and rifampicin. Slow acetylators had a significantly greater increase in total bilirubin level (p=0.011) compared to intermediate acetylators. Loss of appetite was more often observed in fast acetylators than in intermediate acetylators (p=0.021).Conclusions. The obtained data suggest interrelation between the slow type of NAT2 acetylation and the risk of ADRs in patients undergoing pulmonary tuberculosis chemotherapy with isoniazid and rifampicin. Out of all the ADRs registered in the study, the fast acetylators were more likely to have loss of appetite, however, the expansion of the study population is needed to verify this observation. The studied polymorphisms have an impact on the development of ADRs in patients undergoing pulmonary tuberculosis chemotherapy with isoniazid and rifampicin and may be used to predict the safety profile of pharmacotherapy in this group of patients.