Genetic variants of acetylation of organic compounds in children with leukemia in the East Siberian region

Introduction. The activity of the enzyme of the second phase of xenobiotic detoxification N-acetyltransferase 2 (NAT2) depends on gene polymorphisms, the presence of which is associated not only with the pharmacokinetics of drugs, but also with susceptibility to diseases. There are ethnic features in the distribution of genotypes of single nucleotide polymorphisms (SNPs) of these genes.

Purpose of the study – to determine the structure of the child population of the Irkutsk region according to the type of acetylation of organic compounds and to study the association between the rate of acetylation and the predisposition to the development of leukemia in children.

Materials and methods. 82 children with acute lymphoblastic leukemia and 250 healthy medical college students belonging to the Russian ethnic group were examined. The average age of patients was 5.59 ± 4.57, in the control group – 19.7 ± 1.4 years. The type of acetylation was determined by genotyping SNP rs1495741 of the NAT2 gene by conducting a polymerase chain reaction in real time. The type of acetylation was determined at the Institute of Biomedical Technologies of IGMU. The material for the study is DNA obtained by scraping the buccal epithelium.

Results. In the group of children with leukemia, the frequency of the genotype associated with slow acetylation prevailed and amounted to 53.66 %, patients with intermediate acetylation – 35.37 %, and with the fast type of acetylation – 10.97 %. In the control group, the frequency of the genotype associated with slow acetylation also prevailed and amounted to 56.4 %. The frequency of intermediate acetylation was 38 %, fast – 5.6 %. No deviations in the distribution of genotype frequencies from the expected according to the Hardy–Weinberg distribution were detected (p > 0.05). Based on the results of calculating the odds ratio according to three models of inheritance, no statistically significant results were obtained and no associative relationship was identified between the rate of acetylation of xenobiotics and the development of leukemia in children. When comparing the frequency of prevalence of acetylation types among the control group of this study and adults examined in Eastern Siberia earlier, a predominance of the slow type of acetylation was revealed both among adults and among children (63 % and 56.4 %, respectively), and the fastest type was the rarest: 6 % and 5.6 %, respectively.

Conclusion. Types of acetylation do not affect the risk of developing leukemia and occur with the same frequency in comparison with the population of healthy representatives of the European ethnic group of the East Siberian region. In children with leukemia and in healthy controls, the frequency of the SNP rs1495741 NAT2 allele, corresponding to slow acetylators, is predominant. There is no associative relationship between the rate of acetylation of xenobiotics and the risk of developing leukemia in children. The revealed pharmacogenetic features in healthy residents of the East Siberian region and patients with acute lymphoblastic leukemia should be taken into account when developing preventive and personalized methods of modern medicine.

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