gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1194Research ArticleНОВОСТИ КОЛОПРОКТОЛОГИИNEWS OF COLOPROCTOLOGYИммуносупрессоры в современных подходах к терапии воспалительных заболеваний кишечникаImmunosuppressants in modern approaches to treatment of inflammatory bowel diseasesЩукинаО. Б.SchukinaO. B.

Щукина Оксана Борисовна – кандидат медицинских наук, доцент кафедры гастроэнтерологии и диетологии

191015, Санкт-Петербург, ул. Кирочная, д. 41

burmao@gmail.comХаритоновА. Г.KharitonovA. G.

Харитонов Андрей Геннадьевич – ассистент кафедры гастроэнтерологии и диетологии

ХаритидисА. М.KharitidisA. M.

Харитидис Александра Михайловна – врач-гастроэнтеролог 

ИващенкоТ. Э.IvashchenkoT. E.

Иващенко Татьяна Эдуардовна – доктор биологических наук, профессор

НасыховаЮ. А.NasykhovaYu. A.

Насыхова Юлия Алмазовна – кандидат биологических наук

ГабрусскаяТ. В.GabrusskayaT. V.

Габрусская Татьяна Викторовна – ассистент кафедры поликлинической педиатрии, детский гастроэнтеролог

БарановскийА. Ю.BaranovskyA. Yu.

Барановский Андрей Юрьевич – доктор медицинских наук, профессор, заведующий кафедрой гастроэнтерологии и диетологии

Северо-Западный государственный медицинский университет им. И.И. МечниковаРоссияMechnikov north-western state medical universityRussian FederationГородская клиническая больница № 31, Городской центр диагностики и лечения ВЗКРоссияCity hospital N 31, City center of IBD diagnostics and treatmentRussian FederationНаучно-исследовательский институт акушерства и гинекологии им. Д.О. Отта РАМНРоссияOtt research institute of obstetrics and gynecology, Russian academy of medical scienceRussian FederationСанкт-Петербургский государственный педиатрический медицинский университетРоссияSaint Petersburg state pediatric medical universityRussian Federation2013170520132327178Copyright © Щукина О.Б., Харитонов А.Г., Харитидис А.М., Иващенко Т.Э., Насыхова Ю.А., Габрусская Т.В., Барановский А.Ю., 20132013Щукина О.Б., Харитонов А.Г., Харитидис А.М., Иващенко Т.Э., Насыхова Ю.А., Габрусская Т.В., Барановский А.Ю.Schukina O.B., Kharitonov A.G., Kharitidis A.M., Ivashchenko T.E., Nasykhova Y.A., Gabrusskaya T.V., Baranovsky A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/1194

Цель исследования. Охарактеризовать встречаемость мутаций гена TPMT у больных воспалительными заболеваниями кишечника (ВЗК) с миелосупрессией и оценить значение этих мутаций в прогнозе формирования миелосупрессии у этой категории больных, получающих терапию тиопуринами.Материал и методы. Из общего регистра больных ВЗК были выделены пациенты (n=21), у которых в анамнезе наблюдалось развитие миелотоксичности на фоне приема иммуносупрессоров, для определения аллельных вариантов гена TPMT методом полимеразной цепной реакции.Результаты. Лишь у одного пациента (4,7%) с болезнью Крона, с лейкопенией (3,85·109/л) и тромбоцитопенией (80·109/л), развившимися в отдаленные сроки (61 нед) после начала приема азатиоприна, был выявлен полиморфизм TPMT*3A, характеризующийся точечными мутациями 460 G>A и 719A>G. Во всех остальных случаях (20 больных) был найден аллельный вариант TPMT*1 с нормальной продукцией ферментаВыводы. Отсутствует необходимость исследования генетических мутаций перед назначением тиопуринов, однако применение эффективных методов оценки прогноза развития миелотоксичности остается актуальной проблемой. Требуется тщательный контроль лабораторных показателей миелосупрессии в течение терапии тиопуринами. В случае их непереносимости или возникновения миелотоксичности назначают метотрексат.

Aim of investigation

Aim of investigation. To characterize frequency of TPMT gene mutations in patients with inflammatory bowel diseases (IBD) with myelosuppression and to estimate value of these mutations in prognosis of myelosuppression development in patients receiving thiopurine treatment.

Material and methods

Material and methods. From general register of IBD patients, those with bone marrow toxicity on a background of immunosuppressants in past history (n=21) were selected for assessment of TPMT gene allelic variants by polymerase chain reaction.

Results

Results. Only in one patient (4,7%) with Crohn's disease and leukopenia (3,85·109/l) and thrombocytopenia (80·109/l), developed in the remote terms (61 wks) after onset of azathioprin intake, TPMT*3A polymorphism has been revealed, as point mutations 460 G> A and 719A>G. In all other cases (20 patients) allelic variant TPMT*1 with normal enzyme production have been found.

Conclusions

Conclusions. There is no need of study for genetic mutations before prescription of thiopurines, however application of effective methods of evaluation of prognosis of bone marrow toxicity development remains an actual issue. Careful control of laboratory parameters of myelosuppression during treatment by thiopurines is required. In case of intolerance or bone marrow toxicity at intake of thiopurines methotrexate should be prescribed.

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