Prevalence of polymorphisms in N-acetyltransferase 2 gene among patients of Yakut ethnicity newly diagnosed with pulmonary tuberculosis
- Authors: Krasnova N.M.1, Alekseeva E.A.2, Rudykh Z.A.3, Chertovskykh Y.V.2, Klimova T.M.1, Efremova E.N.4, Kravchenko A.F.4, Val N.S.4, Suvorova O.A.5, Suleymanov S.S.6, Vengerovsky A.I.7, Sychev D.A.5
- Affiliations:
- M.K. Ammosov North-Eastern Federal University, Medical Institute
- Republican Hospital no. 3, Center for Personalized Medicine
- Republican Hospital no. 3, Center for Personalized Medicine, Yakutsk, Russia
- Phthisiatry Research-Practice Center
- Russian Medical Academy of Continuous Professional Education
- SAIKO Russian-Japanese Medical Center
- Siberian State Medical University
- Issue: Vol 75, No 2 (2020)
- Pages: 154-161
- Section: PHTHISIOLOGY: CURRENT ISSUES
- URL: https://vestnikramn.spr-journal.ru/jour/article/view/1217
- DOI: https://doi.org/10.15690/vramn1217
- Cite item
Abstract
Background. Tuberculosis therapy can lead to considerably dissimilar outcomes among individual patients. Some patients benefit from anti-tuberculosis chemotherapy leading to a desired therapeutic effect, while other patients show insufficient or absent response, or develop adverse side effects. Individual response to isoniazid is affected by mutations in the gene encoding N-acetyltransferase 2 (NAT2). Wide variations were observed in distributions of polymorphic NAT2 alleles in human populations depending on race, ethnicity, or geographical origin. No data are available to date on prevalence of NAT2 gene polymorphic variants and acetylation types in Yakut (Sakha) patients with newly diagnosed pulmonary tuberculosis.
Aims: the frequencies of NAT2 polymorphic SNPs as well isoniazid acetylation phenotypes were evaluated in the patient’s cohort of Yakut ethnicity with newly diagnosed pulmonary tuberculosis (PTB). The comparison with, other ethnic groups of Asian origin was done.
Methods. Cross-sectional study was conducted among Yakut patient cohorts with newly identified pulmonary tuberculosis. Using real-time PCR the following SNPs were explored: NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), NAT2*13 (rs1041983, C282T). Genetically determined metabolic rates were calculated using NATpred online tool.
Results. NAT2 SNPs were assessed, namely *5, *6, *7, *11, *12, and *13. The most frequent in Yakut patients were NAT2*6 and NAT2*13 SNPs (40.9% and 64.4%, respectively). Significant differences were detected in frequencies of NAT2 *5, *11, *12 polymorphisms; all studied NAT2 gene polymorphisms showed meaningful differences in genotype and minor allele prevalence rates after comparison between Yakut population and other Mongoloid ethnic groups (populations of China, Japan, Vietnam). High prevalence of intermediate acetylation type among ethnic Yakuts (58.3%) was established.
Conclusions. Certain distinct differences in allelic variants of NAT2 gene and acetylation type prevalence in patients of Yakut ethnic origin newly diagnosed with pulmonary tuberculosis let conclude that the existing genotyping and phenotyping data from studies among other Mongoloid populations cannot be implicitly extrapolated on Yakut people. Pharmacogenetic data on individual response to drugs in Yakut patients should be made use of in clinical practice, to develop personalized isoniazid administration algorithms, with a final goal to make treatment more effective and safe.
Full Text

About the authors
Nataliya M. Krasnova
M.K. Ammosov North-Eastern Federal University, Medical Institute
Author for correspondence.
Email: krasnova14@mail.ru
ORCID iD: 0000-0002-4811-7801
SPIN-code: 8703-8169
Russian Federation, 58, Belinsky Street, Yakutsk, 677000
MD, PhD
Elizaveta A. Alekseeva
Republican Hospital no. 3, Center for Personalized Medicine
Email: elizavetaalal@mail.ru
ORCID iD: 0000-0001-6116-5720
SPIN-code: 8918-7035
Russian Federation, 677027, Sakha Republic (Yakutia), Yakutsk, Gorkogo str., 94
biologist
Zoya A. Rudykh
Republican Hospital no. 3, Center for Personalized Medicine, Yakutsk, Russia
Email: vitae003@rambler.ru
ORCID iD: 0000-0001-8212-0150
SPIN-code: 4930-4297
Russian Federation, 677027, Sakha Republic (Yakutia), Yakutsk, Gorkogo str., 94
clinical pharmacologist
Yana V. Chertovskykh
Republican Hospital no. 3, Center for Personalized Medicine
Email: yana_chertovski@mail.ru
ORCID iD: 0000-0003-0941-8633
SPIN-code: 8485-9530
Russian Federation, 677027, Sakha Republic (Yakutia), Yakutsk, Gorkogo str., 94
clinical pharmacologist, Head of the Center for Personalized Medicine
Tatiana M. Klimova
M.K. Ammosov North-Eastern Federal University, Medical Institute
Email: biomedykt@mail.ru
ORCID iD: 0000-0003-2746-0608
SPIN-code: 2635-0865
Russian Federation, 58, Belinsky Street, Yakutsk, 677000
MD, PhD, associate professor of the Department for pharmacology and pharmacy, Medical Institute
Efrosiniya N. Efremova
Phthisiatry Research-Practice Center
Email: efremovaen@tub.ykt.ru
ORCID iD: 0000-0001-6934-2971
SPIN-code: 3688-9742
Russian Federation, 677000, Sakha Republic (Yakutia), Yakutsk, Petra Alekseeva str., 93
TB clinician
Aleksandr F. Kravchenko
Phthisiatry Research-Practice Center
Email: kravchenkoaf@tub.ykt.ru
ORCID iD: 0000-0002-9210-3407
SPIN-code: 3188-6796
Russian Federation, 677000, Sakha Republic (Yakutia), Yakutsk, Petra Alekseeva str., 93
MD, PhD, Professor, Director
Natalia S. Val
Phthisiatry Research-Practice Center
Email: yniit@mail.ru
ORCID iD: 0000-0003-2910-1895
Russian Federation, 677000, Sakha Republic (Yakutia), Yakutsk, Petra Alekseeva str., 93
MD, PhD, Deputy director for medical service
Olga A. Suvorova
Russian Medical Academy of Continuous Professional Education
Email: olga.a.suvorova@mail.ru
ORCID iD: 0000-0001-9661-7213
Russian Federation, 2/1, Barrikadnaya st., Moscow, 125993
Salavat Sh. Suleymanov
SAIKO Russian-Japanese Medical Center
Email: suleymanov-sh@mail.ru
ORCID iD: 0000-0002-3176-2716
SPIN-code: 9047-1399
Russian Federation, Khabarovsk
MD, PhD, Professor
Aleksandr I. Vengerovsky
Siberian State Medical University
Email: pharm-sibgmu@rambler.ru
ORCID iD: 0000-0001-5094-3742
SPIN-code: 8818-0543
Russian Federation, 2, Moscowski Trakt, Tomsk, 634050
MD, PhD, Professor
Dmitry A. Sychev
Russian Medical Academy of Continuous Professional Education
Email: dmitrysychevrmapo@gmail.com
ORCID iD: 0000-0002-4496-3680
SPIN-code: 4525-7556
Russian Federation, 2/1, Barrikadnaya st., Moscow, 125993
MD, PhD, Professor
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