Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia)
Aim. To assess the variability of the NAT2 gene and to comparatively analyze the prevalence of NAT2 polymorphisms and acetylation types among Yakut and Russian patients newly diagnosed with pulmonary tuberculosis (TB), permanently residing in the Sakha Republic (Yakutia).Materials and methods. The s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Siberian State Medical University (Tomsk)
2021-01-01
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| Series: | Бюллетень сибирской медицины |
| Subjects: | |
| Online Access: | https://bulletin.ssmu.ru/jour/article/view/4156 |
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| author | N. M. Krasnova E. N. Efremova A. A. Egorova O. I. Filippova Y. V. Chertovskikh Z. A. Rudykh E. A. Alekseeva T. E. Tatarinova D. A. Sokorutov N. S. Val M. K. Vinokurova A. F. Karvchenko A. I. Vengerovskii D. A. Sychev |
| author_facet | N. M. Krasnova E. N. Efremova A. A. Egorova O. I. Filippova Y. V. Chertovskikh Z. A. Rudykh E. A. Alekseeva T. E. Tatarinova D. A. Sokorutov N. S. Val M. K. Vinokurova A. F. Karvchenko A. I. Vengerovskii D. A. Sychev |
| author_sort | N. M. Krasnova |
| collection | DOAJ |
| description | Aim. To assess the variability of the NAT2 gene and to comparatively analyze the prevalence of NAT2 polymorphisms and acetylation types among Yakut and Russian patients newly diagnosed with pulmonary tuberculosis (TB), permanently residing in the Sakha Republic (Yakutia).Materials and methods. The study included 197 patients with newly diagnosed pulmonary TB (132 Yakuts and 65 Russians) aged (43.3 ± 14.4). The following single-nucleotide polymorphisms were analyzed, using real-time polymerase chain reaction (PCR): NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), and NAT2*13 (rs1041983, C282T). Genetically determined basal metabolic rates were calculated using the NATpred online tool.Results. 75% of residents, both of Yakut and Russian ethnicity, were identified as carriers of NAT2 polymorphic variants known to be related to isoniazid biotransformation. NAT2*6 and *13 allelic variants were more frequent in Yakuts (occurring in 40.9% and 64.4%, respectively); variants NAT2*5, *6, *11, *12, and *13 were more common in Russians (69.2; 55.4; 67.7; 69.2, and 64.6%, respectively). The NAT2*5, *7, *11, and *12 polymorphisms were found to be significantly ethnicity-dependent. The study established substantial prevalence of medium acetylation type (58.3%) in Yakuts and slow acetylation type in Russians (61.5%). Correlations were shown between ethnicity and different prevalence rates of rapid, medium, or slow acetylation types among patients with TB.Conclusion. The observed NAT2 polymorphism distribution patterns and isoniazid acetylation types among Yakut and Russian patients with newly diagnosed pulmonary TB demonstrated that pharmacologic responses can be significantly different between ethnic groups. Findings of pharmacogenetic studies in Yakut and Russian populations should be incorporated in clinical practice for personalized administration of isoniazid. |
| first_indexed | 2024-04-10T01:05:10Z |
| format | Article |
| id | doaj.art-4c8b069261034b5fbc7832841e2d1fde |
| institution | Directory Open Access Journal |
| issn | 1682-0363 1819-3684 |
| language | English |
| last_indexed | 2024-04-10T01:05:10Z |
| publishDate | 2021-01-01 |
| publisher | Siberian State Medical University (Tomsk) |
| record_format | Article |
| series | Бюллетень сибирской медицины |
| spelling | doaj.art-4c8b069261034b5fbc7832841e2d1fde2023-03-13T09:58:26ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842021-01-0119410210910.20538/1682-0363-2020-4-102-1092728Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia)N. M. Krasnova0E. N. Efremova1A. A. Egorova2O. I. Filippova3Y. V. Chertovskikh4Z. A. Rudykh5E. A. Alekseeva6T. E. Tatarinova7D. A. Sokorutov8N. S. Val9M. K. Vinokurova10A. F. Karvchenko11A. I. Vengerovskii12D. A. Sychev13Северо-Восточный федеральный университет (СВФУ) им. М.К. АммосоваНаучно-практический центр (НПЦ) «Фтизиатрия»Научно-практический центр (НПЦ) «Фтизиатрия»Научно-практический центр (НПЦ) «Фтизиатрия»Республиканская клиническая больница (РКБ) № 3Республиканская клиническая больница (РКБ) № 3Республиканская клиническая больница (РКБ) № 3Республиканская клиническая больница (РКБ) № 3Северо-Восточный федеральный университет (СВФУ) им. М.К. АммосоваНаучно-практический центр (НПЦ) «Фтизиатрия»Научно-практический центр (НПЦ) «Фтизиатрия»Научно-практический центр (НПЦ) «Фтизиатрия»Сибирский государственный медицинский университет (СибГМУ)Российская медицинская академия непрерывного профессионального образования (РМАНПО)Aim. To assess the variability of the NAT2 gene and to comparatively analyze the prevalence of NAT2 polymorphisms and acetylation types among Yakut and Russian patients newly diagnosed with pulmonary tuberculosis (TB), permanently residing in the Sakha Republic (Yakutia).Materials and methods. The study included 197 patients with newly diagnosed pulmonary TB (132 Yakuts and 65 Russians) aged (43.3 ± 14.4). The following single-nucleotide polymorphisms were analyzed, using real-time polymerase chain reaction (PCR): NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), and NAT2*13 (rs1041983, C282T). Genetically determined basal metabolic rates were calculated using the NATpred online tool.Results. 75% of residents, both of Yakut and Russian ethnicity, were identified as carriers of NAT2 polymorphic variants known to be related to isoniazid biotransformation. NAT2*6 and *13 allelic variants were more frequent in Yakuts (occurring in 40.9% and 64.4%, respectively); variants NAT2*5, *6, *11, *12, and *13 were more common in Russians (69.2; 55.4; 67.7; 69.2, and 64.6%, respectively). The NAT2*5, *7, *11, and *12 polymorphisms were found to be significantly ethnicity-dependent. The study established substantial prevalence of medium acetylation type (58.3%) in Yakuts and slow acetylation type in Russians (61.5%). Correlations were shown between ethnicity and different prevalence rates of rapid, medium, or slow acetylation types among patients with TB.Conclusion. The observed NAT2 polymorphism distribution patterns and isoniazid acetylation types among Yakut and Russian patients with newly diagnosed pulmonary TB demonstrated that pharmacologic responses can be significantly different between ethnic groups. Findings of pharmacogenetic studies in Yakut and Russian populations should be incorporated in clinical practice for personalized administration of isoniazid.https://bulletin.ssmu.ru/jour/article/view/4156якутырусскиетуберкулезизониазидфармакогенетикаполиморфизмnat2медленныйбыстрыйпромежуточныйтип ацетилирования |
| spellingShingle | N. M. Krasnova E. N. Efremova A. A. Egorova O. I. Filippova Y. V. Chertovskikh Z. A. Rudykh E. A. Alekseeva T. E. Tatarinova D. A. Sokorutov N. S. Val M. K. Vinokurova A. F. Karvchenko A. I. Vengerovskii D. A. Sychev Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) Бюллетень сибирской медицины якуты русские туберкулез изониазид фармакогенетика полиморфизм nat2 медленный быстрый промежуточный тип ацетилирования |
| title | Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) |
| title_full | Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) |
| title_fullStr | Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) |
| title_full_unstemmed | Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) |
| title_short | Comparative analysis of N-acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the Sakha Republic (Yakutia) |
| title_sort | comparative analysis of n acetyltransferase 2 genotyping results among patients with newly diagnosed pulmonary tuberculosis residing in the sakha republic yakutia |
| topic | якуты русские туберкулез изониазид фармакогенетика полиморфизм nat2 медленный быстрый промежуточный тип ацетилирования |
| url | https://bulletin.ssmu.ru/jour/article/view/4156 |
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