ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2019.68.05ymj-1141Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHМежэтнические различия распределения частоты аллелей и генотипов полиморфных вариантов гена NAT2 у больных туберкулезом органов дыханияEthnic differences in distributions of allelic and genotypic frequencies of NAT2 polymorphic variants in patients with pulmonary tuberculosishttps://orcid.org/0000-0002-4811-7801КрасноваН. М.KrasnovaN. M.

Краснова Наталия Михайловна – к.м.н., доцент МИ

Cand.Sci. (Medicine), associate professor of the Department for hospital therapy, clinical pharmacology and occupational diseases

Yakutsk, Republic Sakha (Yakutia)

krasnova14@mail.ruФёдоровА. И.FedorovA. I.

Фёдоров Афанасий Иванович – к.б.н., с.н.с. НИЦ, доцент МИ

Cand.Sci. (Biology), senior researcher, Research center, Medical Institute

associate professor of the Department for public health and health care, general hygiene, and bioethics

Yakutsk, Republic Sakha (Yakutia)

СувороваО. А.SuvorovaO. A.

Суворова Ольга Александровна – студентка

https://orcid.org/0000-0002-9210-3407КравченкоА. Ф.KravchenkoA. F.

Кравченко Александр Федорович – д.м.н., директор

Dr.Sci. (Medicine), Director

ЕвдокимоваН. Е.EvdokimovaN. E.

Евдокимова Надежда Евстафьевна – врач фтизиатр

TB clinician

ЕфремоваЕ. Н.EfremovaE. N.

Ефремова Ефросинья Николаевна – врач фтизиатр

TB clinician, Pulmonary tuberculosis department

ЧертовскихЯ. В.HertovskykhYa. V.

Чертовских Яна Валерьевна – гл. внештат. клинический фармаколог МЗ РС(Я), зав.

Chief non-staff clinical pharmacologist of the Ministry of Health of the Sakha Republic (Yakutia), Head of the Center for Personalized Medicine

АлексееваЕ. А.AlekseevaE. A.

Алексеева Елизавета Александровна – биолог

biologist, Genetic laboratory, Center for Personalized Medicine

РудыхЗ. А.RudykhZ. A.

Рудых Зоя Александровна – врач

clinical pharmacologist, Center for Personalized Medicine

ВасильеваО. Л.VasilievaO. L.

Васильева Ольга Лукинична – врач клинический фармаколог

Clinical pharmacologist, Center for Personalized Medicine

Moscow

https://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич – д.м.н., проф., член-корр. РАН, проф. РАН, ректор

Dr.Sci.(Medicine), Prof., Corresponding Member of the Russian Academy of Sciences, Professor of the Russian Academy of Sciences, Principal

СВФУ им. М.К. АммосоваРоссияMedical Institute, M.K. Ammosov NorthEastern Federal UniversityRussian FederationФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава РоссииРоссияI.M. Sechenov First Moscow State Medical UniversityRussian FederationНПЦ «Фтизиатрия»РоссияPhtisiatry ResearchPractice CenterRussian FederationНПЦ «Фтизиатрия»РоссияPhtisiatry Research-Practice CenterRussian FederationНПЦ «Фтизиатрия»РоссияPhtisiatry Research Practice CenterRussian FederationЦентр персонализированной медицины «Республиканской больницы №3»РоссияRepublican Hospital No.3Russian FederationЦентр персонализированной медицины РБ №3РоссияRepublican Hospital No.3Russian FederationФГБОУ ДПО РМАНПО Минздрава РоссииРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation201929082025042225Copyright © Краснова Н.М., Фёдоров А.И., Суворова О.А., Кравченко А.Ф., Евдокимова Н.Е., Ефремова Е.Н., Чертовских Я.В., Алексеева Е.А., Рудых З.А., Васильева О.Л., Сычев Д.А., 20252025Краснова Н.М., Фёдоров А.И., Суворова О.А., Кравченко А.Ф., Евдокимова Н.Е., Ефремова Е.Н., Чертовских Я.В., Алексеева Е.А., Рудых З.А., Васильева О.Л., Сычев Д.А.Krasnova N.M., Fedorov A.I., Suvorova O.A., Kravchenko A.F., Evdokimova N.E., Efremova E.N., Hertovskykh Y.V., Alekseeva E.A., Rudykh Z.A., Vasilieva O.L., Sychev D.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/1141

Изучены межэтнические различия частоты аллелей и распределения генотипов полиморфных вариантов гена NAT2 (NAT2*5, NAT2*6, NAT2*7) среди этнических групп якутов и русских с впервые выявленным туберкулезом органов дыхания. В результате исследования впервые была установлена частота аллелей и генотипов полиморфных вариантов гена NAT2 (NAT2*5, *6, *7) среди этнических групп якутов и русских, постоянно проживающих на территории РС(Я). Определена распространённость полиморфизмов NAT2*5, *6, *7 среди якутов и русских. Выявлены межэтнические различия частоты аллелей и распределения генотипов полиморфных вариантов rs1801280 (341T>C), rs1799930 (590G>A) и rs1799931 (857G>A) гена NAT2.

Ethnic differences in allele frequencies and genotype distribution for polymorphic variants of NAT2 gene (NAT2*5, NAT2*6, NAT2*7) were studied among ethnic Yakuts and Russians with newly diagnosed pulmonary tuberculosis. This is the first study to establish allele and genotype frequencies for polymorphic variants of NAT2 gene (NAT2*5, *6, *7) among ethnic Yakuts and Russians, who permanently reside in the Sakha Republic (Yakutia). Prevalence of NAT2*5, *6, *7 polymorphisms among Yakuts and Russians was determined, and ethnic differences were shown in allele frequencies and genotype distribution of NAT2 polymorphic variants: rs1801280 (341T>C), rs1799930 (590G>A), and rs1799931 (857G>A).

полиморфизм гена NAT2туберкулезнежелательные побочные реакцииNAT2 gene polymorphismtuberculosisadverse drug effectsReferencesВариабельность фенотипа N-ацетилтрансферазы у жителей г. Гомеля и Гомельской области / Т.В. Сатырова [и др.] // Проблемы здоровья и экологии. – 2010. – № 1 (23). – С. 73–77.Variability of N-acetyltransferase phenotype in the citizens of Gomel and Gomel region / T.V. Satyrova, E.I. Mihailova, A.N. Osipenko [et al.] // Problems of health and ecology. -2010. -№1 (23). – P.73-77.Казаков Р.Е. Фармакогенетика и клинические исследования: точки соприкосновения / Р.Е. Казаков, Н.Г. Бердникова, Д.А. Сычёв // Фармакогенетика и фармакогеномика. – 2016. – № 1. – С. 18–23.Kazakov R.E. Pharmacogenetics and clinical studies: common ground / R.E. Kazakov, N.G. Berdnikova, D.A. Sychev //Pharmacogenetics & pharmacogenomics. – 2016. – № 1. – P. 18–23.Нежелательные побочные реакции на противотуберкулезные препараты основного ряда / Н.А. Степанова [и др.] // Туберкулез и болезни легких. – 2016. – Т. 94, № 5. – С. 42–45. doi: 10.21292/2075-1230-2016-94-5-42-45.Unfavorable side effects to first line anti-tuberculosis drugs / N.A. Stepanova [et al.] //Tuberculosis and Lung Diseases. – 2016. – V. 94. – № 5. – P. 42–45.Показатели по туберкулезу в Российской Федерации 2008-2017 гг.: сайт Федерального государственного бюджетного учреждения Центральный научно-исследовательский институт организации и информатизации здравоохранения МЗиСР РФ. [Электронный ресурс]. – Режим доступа: URL: http://old.mednet.ru/ru/czentr-monitoringa-tuberkuleza.html (дата обращения 08.06.2019г).Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation. Indicators for tuberculosis in Russian Federation 2008-2017. URL: https://mednet.ru/images/materials/CMT/2018_god_tuberkulez_epidsituaciya.pdf. (accessed 8 June 2019).Arylamine N-Acetyltransferase 2 (NAT2) Genetic Diversity and Traditional Subsistence: A Worldwide Population Survey / A. Sabbagh [et al.] // PLoS One. – 2011. – Vol.4, № 6. Available from:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018507 (accessed 20 June 2019). doi.org/10.1371/journal.pone.0018507.Arylamine N-Acetyltransferase 2 (NAT2) Genetic Diversity and Traditional Subsistence: A Worldwide Population Survey / A. Sabbagh [et al.] // PLoS One. – 2011. – Vol.4, № 6. Available from:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018507 (accessed 20 June 2019). doi.org/10.1371/journal.pone.0018507.Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients / SL. Chan [et al.] // PLoS One. – 2017. – Vol. 12, № 10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642896/pdf/pone.0186200.pdf (accessed 20 June 2019). doi: 10.1371/journal.pone.0186200.Association and clinical utility of NAT2 in the prediction of isoniazid-induced liver injury in Singaporean patients / SL. Chan [et al.] // PLoS One. – 2017. – Vol. 12, № 10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642896/pdf/pone.0186200.pdf (accessed 20 June 2019). doi: 10.1371/journal.pone.0186200.Correlation of N-Acetyltransferase 2 Genotype with Isoniazid Acetylation in Polish Tuberculosis Patients / J. Jagodziński [et al.] // Biomed Res. Int. – 2013. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24383060 (accessed 6 June 2019) doi: 10.1155/2013/853602.Correlation of N-Acetyltransferase 2 Genotype with Isoniazid Acetylation in Polish Tuberculosis Patients / J. Jagodziński [et al.] // Biomed Res. Int. – 2013. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24383060 (accessed 6 June 2019) doi: 10.1155/2013/853602.Determining the relation between N-acetyltransferase-2 acetylator phenotype and antituberculosis drug induced hepatitis by molecular biologic tests / V. BozokCetintaş [et al.] // TuberkToraks. – 2008. – Vol. 56, № 1. – P. 81–86.Determining the relation between N-acetyltransferase-2 acetylator phenotype and antituberculosis drug induced hepatitis by molecular biologic tests / V. BozokCetintaş [et al.] // TuberkToraks. – 2008. – Vol. 56, № 1. – P. 81–86.Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis / SH. Kim [et al.] // Pharmacogenomics. – 2009. – Vol. 10, № 11. – P. 1767–1779. doi: 10.2217/pgs.09.100.Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis / SH. Kim [et al.] // Pharmacogenomics. – 2009. – Vol. 10, № 11. – P. 1767–1779. doi: 10.2217/pgs.09.100.Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies/ H. Tang [et al.] // Am J Hum Genet. – 2005. – Vol. 76, № 2. – P. 268–275.Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies/ H. Tang [et al.] // Am J Hum Genet. – 2005. – Vol. 76, № 2. – P. 268–275.Hein D. W. N-acetyltransferase 2 genetic polymorphism : effects of carcinogen and haplotype on urinary bladder cancer risk / D. W. Hein // Oncogene. – 2006. – Vol. 25, № 11. – P.1649–1658.Hein D. W. N-acetyltransferase 2 genetic polymorphism : effects of carcinogen and haplotype on urinary bladder cancer risk / D. W. Hein // Oncogene. – 2006. – Vol. 25, № 11. – P.1649–1658.Jarrar YB. Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian volunteers / YB Jarrar, AA Balasmeh, W Jarrar // Libyan J Med. – 2018 – Vol. 13, № 1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717714/–1408381 (accessed 1 June 2019). doi: 10.1080/19932820.2017.1408381.Jarrar YB. Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian volunteers / YB Jarrar, AA Balasmeh, W Jarrar // Libyan J Med. – 2018 – Vol. 13, № 1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717714/–1408381 (accessed 1 June 2019). doi: 10.1080/19932820.2017.1408381.Kurose K. Population differences in major functional polymorphisms of pharmacokinetics / pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development / K. Kurose, E. Sugiyama, Y. Saito // Drug MetabPharmacokinet. – 2012. – Vol. 27, №1. – P. 9–54.Kurose K. Population differences in major functional polymorphisms of pharmacokinetics / pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development / K. Kurose, E. Sugiyama, Y. Saito // Drug MetabPharmacokinet. – 2012. – Vol. 27, №1. – P. 9–54.Low N-acetyltransferase 2 activity in isoniazid-associated acute hepatitis requiring liver transplantation / JP. Cramer [et al.] // Transpl Int. – 2010. – Vol. 23, № 2. – P. 231–233. doi: 10.1111/j.1432-2277.2009.00921.x.Low N-acetyltransferase 2 activity in isoniazid-associated acute hepatitis requiring liver transplantation / JP. Cramer [et al.] // Transpl Int. – 2010. – Vol. 23, № 2. – P. 231–233. doi: 10.1111/j.1432-2277.2009.00921.x.Ma Q. Pharmacogenetics, pharmacogenomics, and individualized medicine / Q Ma, A.Y. Lu // Pharmacol Rev. – 2011. – Vol. 63, № 2. – P. 437–459. doi: 10.1124/pr.110.003533Ma Q. Pharmacogenetics, pharmacogenomics, and individualized medicine / Q Ma, A.Y. Lu // Pharmacol Rev. – 2011. – Vol. 63, № 2. – P. 437–459. doi: 10.1124/pr.110.003533Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1,MTHFR,MTRR, NQO1,NAT2, HLADQA-1,and AB0 allele frequencies in native Russians / O. Gra [et al.] // Genet Test Mol Biomarkers. – 2010. – Vol. 14, № 3. – P. 329–342. doi: 10.1089/gtmb.2009.0158.Microarray-based detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1,MTHFR,MTRR, NQO1,NAT2, HLADQA-1,and AB0 allele frequencies in native Russians / O. Gra [et al.] // Genet Test Mol Biomarkers. – 2010. – Vol. 14, № 3. – P. 329–342. doi: 10.1089/gtmb.2009.0158.NAT2 and CYP2E1 polymorphisms associated with antituberculosis drug-induced hepatotoxicity in Chinese patients / HR. An [et al.] // Clin Exp Pharmacol Physiol. – 2012. – Vol. 39, № 6. – P. 535–543. doi: 10.1111/j.1440-1681.2012.05713.x.NAT2 and CYP2E1 polymorphisms associated with antituberculosis drug-induced hepatotoxicity in Chinese patients / HR. An [et al.] // Clin Exp Pharmacol Physiol. – 2012. – Vol. 39, № 6. – P. 535–543. doi: 10.1111/j.1440-1681.2012.05713.x.NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris / R. Dursun [et al.] //Biomed Res Int. – 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=NAT2+Gene+Polymorphisms+in+Turkish+Patients+with+Psoriasis+Vulgaris (accessed 15 June 2019) doi: 10.1155/2018/3258708.NAT2 Gene Polymorphisms in Turkish Patients with Psoriasis Vulgaris / R. Dursun [et al.] //Biomed Res Int. – 2018. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=NAT2+Gene+Polymorphisms+in+Turkish+Patients+with+Psoriasis+Vulgaris (accessed 15 June 2019) doi: 10.1155/2018/3258708.Pharmacogenomics Knowledge for Personalized Medicine / Whirl-Carrillo [et al.] // Clinical Pharmacology & Therapeutics. – 2012. – Vol. 92, № 4. – P. 414–417. doi: 10.1038/clpt.2012.96Pharmacogenomics Knowledge for Personalized Medicine / Whirl-Carrillo [et al.] // Clinical Pharmacology & Therapeutics. – 2012. – Vol. 92, № 4. – P. 414–417. doi: 10.1038/clpt.2012.96PharmGKB Summary: Isoniazid Pathway, Pharmacokinetics / Daniel J. Klein [et al.] // Pharmacogenet Genomics. – 2016. – Vol. 26, № 9. – P. 436–444. doi: 10.1097/FPC.0000000000000232PharmGKB Summary: Isoniazid Pathway, Pharmacokinetics / Daniel J. Klein [et al.] // Pharmacogenet Genomics. – 2016. – Vol. 26, № 9. – P. 436–444. doi: 10.1097/FPC.0000000000000232Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis / L Ben Mahmoud [et al.] // PatholBiol (Paris). – 2012. – Vol. 60, № 5. – P. 324–330. doi: 10.1016/j.patbio.2011.07.001.Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis / L Ben Mahmoud [et al.] // PatholBiol (Paris). – 2012. – Vol. 60, № 5. – P. 324–330. doi: 10.1016/j.patbio.2011.07.001.The Pharmacogenetics of NAT2 Enzyme Maturation in Perinatally HIV Exposed Infants Receiving Isoniazid / R. Zhu [et al.] // J Clin Pharmacol. – 2009. – Vol. 6, №11. – P. 1249–1254.The Pharmacogenetics of NAT2 Enzyme Maturation in Perinatally HIV Exposed Infants Receiving Isoniazid / R. Zhu [et al.] // J Clin Pharmacol. – 2009. – Vol. 6, №11. – P. 1249–1254.Tuberculosis Pharmacogenetics: State of The Art (March 20th 2013) / Raquel Lima de Figueiredo Teixeira [et al.] // Tuberculosis - Current Issues in Diagnosis and Management Available from: https://www.intechopen.com/books/tuberculosis-current-issues-in-diagnosis-and-management/tuberculosis-pharmacogenetics-state-of-the-art (accessed 5 June 2019). doi: 10.5772/54984.Tuberculosis Pharmacogenetics: State of The Art (March 20th 2013) / Raquel Lima de Figueiredo Teixeira [et al.] // Tuberculosis - Current Issues in Diagnosis and Management Available from: https://www.intechopen.com/books/tuberculosis-current-issues-in-diagnosis-and-management/tuberculosis-pharmacogenetics-state-of-the-art (accessed 5 June 2019). doi: 10.5772/54984.

The authors declare that there are no conflicts of interest present.