The risk of anti-tuberculosis (ATB) drug-induced liver injury could be determined by genotype polymorphism of the xenobiotic-metabolizing enzymes. The aim of presented research was the investigation of an impact of CYP3A4*1G polymorphism on liver function in patients with TB during anti-tuberculosis therapy. There were analyzed case histories of 105 patients with newly diagnosed pulmonary TB at Odessa Regional TB Hospital in 2012-2014. We have considered their medical records at the beginning and at the end of inpatient treatment including activity of biochemical indices such as total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutathione transferase (GGT). The genotype CYP3A4*1G, 20230G>A was detected by PCR. At the beginning of the treatment the level of studied biochemical indices was almost the same regardless of CYP3A4*1G genotype. After the conducted in-patient treatment the biochemical indices in fast metabolizers insignificantly increased, while the level of bilirubin dropped by 10.4% (p<0.05). In slow metabolizers after in-patient treatment the serum total bilirubin level increased by 8.0% (p<0.05), the activity of ALT raised by 67.2% (p<0.05), AST – by 37.4% (p>0.05), also the number of the patients with ALT and AST level beyond normal almost doubled. After completion of in-patient treatment in moderate and slow metabolizers serum GGT activity increased by 2.5 times (p<0.05) and 1.3 times (p>0.05) correspondently, among fast metabolizers – on the contrary, the number of the individuals with increased GGT level dropped (p<0.05). Thus in slow metabolizers according to CYP3A4*1G genotype after completion of in-patient stage of anti-TB treatment the level of cytolysis and toxicity indexes was much higher than in fast metabolizers. That is why detection of CYP3A4*1G genotype of 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.
Objective. To determine the predictive value of the genetic polymorphism of the N-arylacetyltransferase-2 (NAT-2) gene for assessing the risk of postoperative adhesive intestinal obstruction in children. Methods. In all children (36 children with adhesive intestinal obstruction (main group) and 35 planned patients (comparative group)) the acetylation genotype was studied by detecting point mutations of the NAT-2 gene using allele-specific amplification method with analysis of apolymerase chain reaction-restrictionfragmentlengthpolymorphism. Results. The study of the frequency of mutations at position 481 revealed the greatest diversity of the studied variants of genotypes: 33.3% of the children of the main group were homozygous for the wild-type gene, 44.4% were heterozygotes, 22.2% of patients had a homozygous mutant gene. According to the NAT-2 * 6A genotype (G 590 - A), the majority of patients (55.6%) were heterozygotes, 44.4% were homozygotes with the wild-type of the gene. Not a single case of mutation at position 857 has been identified. Among the children of the main group, the share of «fast» acetylators was 69.4%, in the comparison group - 40.0% (χ<sup>2</sup>=6.215; p=0.013). The development of postoperative adhesive intestinal obstruction in children with the “fast” acetylation genotype occurred in the absence of clinical and anamnestic risk factors and was characterized by a greater severity and prevalence of intra-abdominal adhesive process (PAI was (14.8±1.8) and (8.1±2.4 ), respectively). Conclusion. The risk of developing postoperative adhesive complications in children can be done preventively by determining the genetic polymorphism of the N-acetyltransferase-2 gene. The risk group for developing adhesive intestinal obstruction is made up of children who are the carriers of NAT-2 alleles and correspond to the genotype of «fast» and «moderate» acetylation. Children who are «fast» acetylators have a more pronounced intra-abdominal adhesion process and a higher risk of complications associated with excessive adhesion even in the absence of other risk factors. What this paper adds N-acetyltransferase 2 (NAT2) gene polymorphism as a prognostic risk factor for the development of adhesive intestinal obstruction in children has been studied. Children as the carriers of the «fast» acetylator genotype have a higher risk of developing intra-abdominal adhesions and therefore require more comprehensive preventive measures at all stages of possible influence.
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