phgenomicsФармакогенетика и фармакогеномикаPharmacogenetics and Pharmacogenomics2588-05272686-8849LLC "Izdatelstvo OKI"10.24411/2588-0527-2019-10040phgenomics-146Research ArticleФАРМАКОГЕНЕТИЧЕСКИЕ ИССЛЕДОВАНИЯPHARMACOGENETICS STUDYРаспространённость полиморфизмов гена NAT2, ассоциированных с изменением скорости биотрансформации изониазида, среди якутских и русских пациентов с туберкулёзомPrevalence of NAT2 polymorphisms and phenotypes associated with the rate of isoniazid biotransformation among Yakutian and Russian tuberculosis patientshttps://orcid.org/0000-0001-9661-7213СувороваО. А.SuvorovaO. A.

Суворова Ольга Александровна - студентка лечебного факультета ФГАОУ ВО Первый МГМУ имени И.М. Сеченова Минздрава России (Сеченовский Университет).

Москва

Suvorova Olga - Student of General Medicine of FSAEI HE I.M. Sechenov First MSMU MOH Russia (Sechenovskiy University).

Moscow

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

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

Якутск

Kravchenko Alexander - PhD, director.

Yakutsk

https://orcid.org/0000-0003-2910-1895ВальН. С.ValN. S.

Валь Наталия Семеновна - к. м. н.

Якутск

Val Natalia - PhD.

Yakutsk

https://orcid.org/0000-0002-4811-7801КрасноваН. М.KrasnovaN. M.

Краснова Наталия Михайловна - к. м. н.

Якутск

Krasnova Natalia - PhD.

Yakutsk

https://orcid.org/0000-0003-0941-8633ЧертовскихЯ. В.ChertovskikhYa. V.

Чертовских Яна Валерьевна - врач.

Якутск

Chertovskikh Yana - doctor.

Yakutsk

https://orcid.org/0000-0001-8212-0150РудыхЗ. А.RudykhZ. A.

Рудых Зоя Александровна - врач.

Якутск

Rudykh Zoya - doctor.

Yakutsk

https://orcid.org/0000-0001-6116-5720АлексееваЕ. А.AlekseevaE. A.

Алексеева Елизавета Александровна - биолог.

Якутск

Alekseeva Elizaveta - biologist.

Yakutsk

https://orcid.org/0000-0001-9726-5715ВасильеваО. Л.VasilevaO. L.

Васильева Ольга Лукична - врач.

Якутск

Vasilieva Olga - doctor.

Yakutsk

https://orcid.org/0000-0002-0187-280XЕвдокимоваН. Е.EvdokimovaN. E.

Евдокимова Надежда Евстафьевна - врач.

Якутск

Evdokimova Nadezhda - doctor.

Yakutsk

https://orcid.org/0000-0002-2295-7167ИващенкоД. В.IvashchenkoD. V.

Иващенко Дмитрий Владимирович - к. м. н. ФГБОУ ДПО РМАНПО Минздрава России: н. с. отдела персонализированной медицины НИИ МПМ; Доцент кафедры детской психиатрии и психотерапии.

Москва

Ivashchenko Dmitriy - PhD; Research Officer Department of Personalized medicine of FSBEI FPE RMACPE MOH Russia; Associate Professor, department of child psychiatry and psychotherapy.

Moscow

dvi1991@yandex.ruhttps://orcid.org/0000-0002-4496-3680СычёвД. А.SychevD. A.

Сычёв Дмитрий Алексеевич - д. м. н., профессор, член-корреспондент РАН, заведующий кафедрой клинической фармакологии и терапии. SPIN-код: 4525-7556

Москва

Sychev Dmitry - MD, Professor, Corresponding Member, Russian Academy of Sciences, Head of department of clinical pharmacology and therapy. SPIN-code: 4525-7556

Moscow

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФ; ФГАОУ ВО Первый МГМУ имени И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияFSBEI FPE RMACPE MOH Russia; FSAEI HE I.M. Sechenov First MSMU MOH Russia (Sechenovskiy University)Russian FederationГБУ РС(Я) «Научно-практический центр «Фтизиатрия»РоссияSBI RS (Ya) «Scientific and Practical Centre of Phthisiology»Russian FederationФГАОУ ВО «Северо-Восточный федеральный университет имени М.К. Аммосова»РоссияNorth-Eastern Federal UniversityRussian FederationЦентр персонализированной медицины, ГБУ РС (Я) «Республиканская больница № 3»РоссияCentre of personalized medicine, SBI RS (Ya) «Republican hospital № 3»Russian FederationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» МЗ РФРоссияFSBEI FPE RMACPE MOH RussiaRussian Federation201923032020013540Copyright © Суворова О.А., Кравченко А.Ф., Валь Н.С., Краснова Н.М., Чертовских Я.В., Рудых З.А., Алексеева Е.А., Васильева О.Л., Евдокимова Н.Е., Иващенко Д.В., Сычёв Д.А., 20192019Суворова О.А., Кравченко А.Ф., Валь Н.С., Краснова Н.М., Чертовских Я.В., Рудых З.А., Алексеева Е.А., Васильева О.Л., Евдокимова Н.Е., Иващенко Д.В., Сычёв Д.А.Suvorova O.A., Kravchenko A.F., Val N.S., Krasnova N.M., Chertovskikh Y.V., Rudykh Z.A., Alekseeva E.A., Vasileva O.L., Evdokimova N.E., Ivashchenko D.V., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacogenetics-pharmacogenomics.ru/jour/article/view/146

Для выявления пациентов с риском неэффективности или нежелательных реакций на стандартные дозы противотуберкулёзных препаратов было предложено использование фармакогенетические исследования генов ферментов, метаболизирующих данные лекарственные средства. Так как частота генотипов варьируется в зависимости от этнической принадлежности пациентов, необходимо проведение исследований среди различных этнических групп. Целью данного исследования было выявить типы и распространённость полиморфизмов и фенотипов изониазид-метаболизирующего фермента NAT2 среди якутов, болеющих туберкулёзом, а также провести сравнительный анализ с русскими пациентами. Всего было прогенотипировано 158 пациентов: 50 были якутами, 41 – русскими, проживающими на территории Якутии, 67 – русскими, проживающими на территории Московской области. Было идентифицировано 6 полиморфизмов NAT2 (*5, *6, *7, *11, *12, *13). Обнаружены значимые отличия в распространёенности NAT2*5, *11, *12 между якутами и русскими, встречаемость данных полиморфных вариантов выше среди русских пациентов. Частота встречаемости быстрого фенотипа среди якутов значимо выше таковой среди русских. Полученные данные могут внести вклад в улучшение эффективности противотуберкулёзной терапии у пациентов из Якутии, основанной на фармакогенетических исследованиях.

To assess the risk of insufficient response or adverse reactions to standard doses of anti-TB drugs, it was proposed to use pharmacogenetic testing of genes of enzymes that metabolize these drugs. Since the frequency of genotypes varies depending on patients’ ethnicity, it is necessary to conduct studies among ethnic groups. The aim of this study was to identify the types of N-acetyltransferase 2 (NAT2) polymorphisms and phenotypes and their prevalence among Yakutian tuberculosis patients, as well as to conduct a comparative analysis with Russian patients. In total 158 patients were examined using real-time PCR: 50 – Yakutians, 41 – Russians (Yakutia), 67 – Russians (Moscow region). Six NAT2 polymorphisms were identified (*5, *6, *7, *11, *12, *13). Significant differences in the distribution of NAT2*5, *11, *12 between Yakutians and Russians were found: these polymorphisms prevail among Russian patients. The frequency of rapid phenotype among Yakutians is higher compared to Russians. The data obtained can contribute to the improvement of the antituberculosis therapy effectiveness in Yakutian patients.

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