NAT2 GENE POLYMORPHISMS IS A RISK FACTOR IN PATIENTSCO-INFECTED WITH HIV AND TUBERCULOSIS
Actuality. The number of human immunodeficiency virus (HIV)-infected patients with active tuberculosis (TB) and multiple/extensive drug resistance has increased in recent years. Backup drugs with high hepatotoxicity are used in the treatment regimens of this category of patients. Identification of markers of adverse events in the form of hepatotoxicity by determining the type of acetylation in patients with HIV infection and TB when prescribing drugs metabolized by NAT2 enzyme may influence the selection of optimal doses and reduce the toxic effect on the liver.
The aim of the research was to determine the features of N-acetyl-transferase 2 (NAT2) gene polymorphisms in HIV-infected patients with active tuberculosis with advanced drug-induced liver damage.
Materials and мethods. NAT2 genotype and haplotype determination was performed in 151 TB/HIV-infected patients receiving drugs with different types of acetylation. Determination of allele frequencies for six single nucleotide polymorphisms (SNPs) of the genotype was used by real-time PCR, allele verification was confirmed by pyrosequencing using the AmpliSense® Pyroskrin PHARMA-screen-2a reagent kit. Analysis was performed using IBM SPSS Statistics 29.0.2.0. significance of differences in frequency distribution of variables was used for Pearson's Chi-square criterion. It was used as a measure of relative risk with a regression confidence interval of 95% and a significance level of 5% (p <0.05). Reliability of differences in median values was determined based on the Mann-Whitney criterion for two groups, the Kraskell-Wallis criterion for multiple comparison of groups (p <0.05).
Results. A larger proportion of patients were found to have a slow type of acetylation (57.6%). Among the haplotypes causing the slow type of acetylation the most frequent were haplotypes NAT2*5B (48.3%) and NAT2*6A (40.2%). The observation showed more frequent increase of aminotransaminase activity from 3 to 10 norms from the upper limit in patients with slow type of acetylation of the NAT2 enzyme gene. They accounted for 43.7% of the total number of identified cases of the slow type of acetylation. The median value of aminotransaminase levels was significantly higher in patients with slow type of acetylation compared to patients in the fast acetylation group (p < 0.0001).
Conclusions. Slow type of acetylation should be considered a high risk factor for hepatotoxicity in TB/HIV patients when prescribed anti-TB drugs. Data on isoniazid acetylation and NAT2 genotypes can be used to improve treatment quality and reduce the risk of isoniazid toxicity in TB treatment.
Keywords. hepatotoxicity, tuberculosis, HIV, acetylation type, isoniazid, NAT2.
Nikitin Igor - Professor, Doctor of Medical science Federal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation; (Orcid ID: 0000-0003-1699-0881), E-mail: igor.nikitin.64@mail.ru, Phone: +79161615727;
Vasilyeva Irina - Phd, Federal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation (неофициально — Pirogov Russian National Research Medical University); (orcid.org/0000-0001-6986-901); E-mail: iv001yt@gmail.com; Phone: +79099409186;
Gaponova Irina - Junior Researcher, Laboratory of Molecular Methods for the Study of Genetic Polymorphisms Central Research Institute of Epidemiology of Rospotrebnadzor; (Orcid ID: 0000-0003-4481-2249); E-mail: gaponova@cmd.su, Phone: +79998743852
Alieva Saule - Ph.D. 3rd year of Federal State Educational Institution of Higher Education "Russian National Research Medical University named after N.I. Pirogov" of the Ministry of Health of the Russian Federation; Clinical pharmacologist NAO MUS Semey, Republic of Kazakhstan; (Orcid ID: 0000-0001-5098-9206); E-mail: asu0507@mail.ru, Phone: +7071650035;
Baiburova Assel - Resident of the 2nd year of study at the Department of Pharmacology named after M.D. Musin NCJSC «Semey Medical University», Semey, Republic of Kazakhstan; (Orcid ID: 0009-0006-3281-2902); E-mail: tukeeva.a_95@mail.ru; Phone:+7755127118;
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Abdul M., Nikitin I.G., Gaponova I.I., Vasilyeva I.V., Alieva S.A., Baiburova A.B. NAT2 Gene polymorphisms is a risk factor in patients Co-infected with HIV and tuberculosis // Nauka i Zdravookhranenie [Science & Healthcare]. 2024. Vol.26 (3), pp. 16-23. doi 10.34689/SH.2024.26.3.002 Абдул М., Никитин И.Г., Гапонова И.И., Васильева И.В., Алиева С.А., Байбурова А.Б. Полиморфизм гена NAT2 – фактор риска у пациентов с ко-инфекцией ВИЧ и туберкулезом // Наука и Здравоохранение. 2024. Т.26 (3). С. 16-23. doi 10.34689/SH.2024.26.3.002 Абдул М., Никитин И.Г., Гапонова И.И., Васильева И.В., Алиева С.А., Байбурова А.Б. NAT2 гені полиморфизмі АҚТҚ-жұқпасы және туберкулезбен қос инфекцияланган науқастардағы тәуекел факторы // Ғылым және Денсаулық сақтау. 2024. Т.26 (3). Б. 16-23. doi 10.34689/SH.2024.26.3.002Авторизируйтесь для отправки комментариев