Abstract:
The aim of this research was to find the meaning of
CYP3A4*1G polymorphism in TB patients for the
toxicity development during inpatient TB treatment.
Figure
Thus according to CYP3A4*1G genotype after
completion of in-patient stage of anti-TB treatment
the intensity of cytolysis and hepatotoxicity indices in
“slow metabolizers” were much higher than in “rapid
metabolizers”. That is why, the detection of
CYP3A4*1G genotype in TB patients at the
beginning of TB treatment could help to recognize
the individuals with high risk of liver injury who need
additional medical care.
This work was supported by the special scientific
research program of the Healthcare Ministry of
Ukraine (№0121U107508).
Results
CYP3A4*1G genotyping of 105 patients has shown
that 91.4% had no mutation in this region (*1/*1
genotype; “rapid metabolizers”), 4.8% had one
mutated allele (*1/*1G genotype; “intermediate
metabolizers”), and 3.8% had both mutated alleles
(*1G/*1G genotype; “slow metabolizers”). At the
beginning of the treatment the level of studied
biochemical indices was almost the same regardless
of CYP3A4*1G genotype. After the conducted inpatient treatment in “rapid metabolizers” studied
biochemical indexes insignificantly increased, while
the level of bilirubin has dropped on 10,4% (p=0,023;
СІ=-2,85…-0,21). In “slow metabolizers” after
inpatient treatment the serum total bilirubin level
increased on 8,0% (p<0,001; СІ=2,33…6,03), the
activity of ALT raised on 67,2% (p=0.033; CI=-
30,14…-1,86), AST - on 37,4% (p>0,05)
comparatively to the initial level; also the amount of
the patients with ALT and AST level beyond normal
almost doubled. In result of inpatient treatment in
“intermediate metabolizers” the activity of serum ALT
and AST increased in 1.5 times (p>0,05). After
completion of inpatient treatment in “intermediate
metabolizers” and in “slow metabolizers” serum GGT
activity increased in 2,5 times (p<0,05) and 1,3 times
(p>0,05) correspondently; among ”rapid
metabolizers” – on the contrary, the number of the
individuals with increased GGT level has dropped
(p<0,05). According to obtained results the presence
of variant alleles (“slow metabolizers” genotype) is
accompanied by slowing down of the conjugation
stage rate in liver that is approved by increasing of
bilirubin level. In addition, this genotype is
associated with more intensive cytolysis of
hepatocytes that is witnessed by raising of ALT and
ACT activity in the blood.
Design Method
Blood samples were obtained from 105 patients with
newly diagnosed pulmonary TB at Odessa Regional
TB Hospital in 2015. The study was approved by
Ethical Commission of Odessa National Medical
University. DNA material was extracted from the blood
using a kit of DNA-Sorb-B. A CYP3A4*1G genotype
was detected with the help of PCR according to Yuan
Gao, et al. 2008. All TB patients were receiving
complex therapy recommended by the World Health
Organization DOTS strategy. We have considered
medical records at the beginning and at the end of
inpatient treatment including activity of biochemical
indices such as alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and gammaglutathione transferase (GGT), and total bilirubin level
in blood serum.
