Keywords
Abstract
Among the measures that can prevent the development of adverse effects of anti-tuberculosis therapy, the correction of pharmacotherapy depending on the genetic characteristics of patients play an important role. It is known that the enzyme cytochrome (CYP) 3A4/5 takes part in the metabolism of one-third of the medicines.
The aim of study was to investigate an impact of CYP3A4 polymorphism on liver function in the patients with pulmonary tuberculosis (TB) during anti-tuberculosis therapy. For this purpose, the PCR-detection of polymorphism of CYP3A4*1B, CYP3A4*1G genes, which determine the activity of CYP3A4 enzyme, was performed in 105 enrolled patients with newly diagnosed pulmonary TB. We have considered their medical records at the beginning and at the end of inpatient treatment including serum activity of biochemical indices such as total bilirubin, alanineaminotransferase (ALАT), aspartateaminotransferase (ASАT), and gamma-glutathione transferase (GGT) activities.
It was established that out of 105 enrolled TB-patients 84 individuals (80.0 %) carried the genotype of «rapid metabolizers», rest – 15 individuals (14.3 %) and 6 individuals (5.7 %) were «intermediate metabolizers» and «slow metabolizers» correspondently. At the beginning of the treatment the highest level
of total bilirubin had been observed in «rapid metabolizers», a little bit lower level of the bilirubin was in «intermediate metabolizers» and «slow metabolizers», furthermore in the last group it was 79.5 % less, than in «rapid metabolizers» (p = 0.047). Initially the highest activity of cytolysis indices – ALAT and ASAT enzymes had been observed in «rapid metabolizers», while the lowest activity – in «slow metabolizers». For instance, the initial ALAT activity in serum in «slow metabolizers» was 43.0 % lower, than in «rapid metabolizers» (p = 0.025). At the end of inpatient treatment the lowering of serum total bilirubin occurred in «rapid metabolizers» and «intermediate metabolizers»; in the same time the opposite tendency – increasing of serum bilirubin on 42,9 % (p < 0,001) appeared in «slow metabolizers». At the end of inpatient treatment, the ALAT and ASAT activity in «rapid metabolizers» and «intermediate metabolizers» has increased insignificantly (p > 0.05). The activity of ASAT and ALAT raised in «slow metabolizers» on 98,9 % (p = 0.025) and on 76,1 % (p > 0.05) correspondently. Thus, the genotype of «slow metabolizers» is a predictor of hepatotoxicity development during anti-tuberculosis therapy. That is why the detection of CYP3A4 genotype in TB patients at the beginning of TB treatment could help to recognize a group of the individuals with increased risk of liver injury during therapy, that in turn allows the doctors to provide timely correction of pharmacotherapy.