Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciences0869-60472414-3545"Paediatrician" Publishers LLC121710.15690/vramn1217Research ArticlePrevalence of polymorphisms in N-acetyltransferase 2 gene among patients of Yakut ethnicity newly diagnosed with pulmonary tuberculosisKrasnovaNataliya M.<p>MD, PhD</p>krasnova14@mail.ruhttps://orcid.org/0000-0002-4811-7801AlekseevaElizaveta A.<p>biologist</p>elizavetaalal@mail.ruhttps://orcid.org/0000-0001-6116-5720RudykhZoya A.<p>clinical pharmacologist</p>vitae003@rambler.ruhttps://orcid.org/0000-0001-8212-0150ChertovskykhYana V.<p>clinical pharmacologist, Head of the Center for Personalized Medicine</p>yana_chertovski@mail.ruhttps://orcid.org/0000-0003-0941-8633KlimovaTatiana M.<p>MD, PhD, associate professor of the Department for pharmacology and pharmacy, Medical Institute</p>biomedykt@mail.ruhttps://orcid.org/0000-0003-2746-0608EfremovaEfrosiniya N.<p>TB clinician</p>efremovaen@tub.ykt.ruhttps://orcid.org/0000-0001-6934-2971KravchenkoAleksandr F.<p>MD, PhD, Professor, Director </p>kravchenkoaf@tub.ykt.ruhttps://orcid.org/0000-0002-9210-3407ValNatalia S.<p>MD, PhD, Deputy director for medical service</p>yniit@mail.ruhttps://orcid.org/0000-0003-2910-1895SuvorovaOlga A.olga.a.suvorova@mail.ruhttps://orcid.org/0000-0001-9661-7213SuleymanovSalavat Sh.<p>MD, PhD, Professor</p>suleymanov-sh@mail.ruhttps://orcid.org/0000-0002-3176-2716VengerovskyAleksandr I.<p>MD, PhD, Professor</p>pharm-sibgmu@rambler.ruhttps://orcid.org/0000-0001-5094-3742SychevDmitry A.<p>MD, PhD, Professor</p>dmitrysychevrmapo@gmail.comhttps://orcid.org/0000-0002-4496-3680M.K. Ammosov North-Eastern Federal University, Medical InstituteRepublican Hospital no. 3, Center for Personalized MedicineRepublican Hospital no. 3, Center for Personalized Medicine, Yakutsk, RussiaPhthisiatry Research-Practice CenterRussian Medical Academy of Continuous Professional EducationSAIKO Russian-Japanese Medical CenterSiberian State Medical University180620207521541610410201926042020Copyright © 2020, "Paediatrician" Publishers LLC2020<p><strong>Background.</strong> 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.</p>
<p><strong>Aims:</strong> the frequencies of NAT2 polymorphic SNPs as well isoniazid acetylation phenotypes were evaluated in the patients cohort of Yakut ethnicity with newly diagnosed pulmonary tuberculosis (PTB). The comparison with, other ethnic groups of Asian origin was done.</p>
<p><strong>Methods.</strong> 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.</p>
<p><strong>Results.</strong> 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.</p>
<p><strong>Conclusions.</strong> 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.</p>yakuttuberculosisisoniazidpharmacogeneticssingle-nucleotide polymorphismhuman NAT2 proteinякутытуберкулезизониазидфармакогенетикаполиморфизмNAT2[https://mednet.ru/. Эпидемическая ситуация по туберкулезу в России [доступ от 08.06.2019]. [https://mednet.ru/. Epidemicheskaya situatsiya po tuberkulezu v Rossii. 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