medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-228Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВлияние однонуклеотидных полиморфизмов генов TNF и LTA на клинические параметры и маркеры воспаления у пациентов с муковисцидозомTNF and LTA gene polymorphisms in cystic fibrosis patients: clinical parameters and inflammatory markersШмаринаГ. В.ShmarinaG. V.sakmarariver@yahoo.comПухальскаяД. А.PukhalskayaD. A.noemail@neicon.ruБукинаА. М.BukinaA. M.noemail@neicon.ruАвакянЛ. В.AvakianL. V.noemail@neicon.ruСемыкинС. Ю.SemykinS. U.noemail@neicon.ruАмелинаЕ. Л.AmelinaE. L.noemail@neicon.ruКрасовскийС. А.KrasovskiyS. A.noemail@neicon.ruУсачеваМ. Ю.UsachevaM. V.noemail@neicon.ruАлешкинВ. А.AlioshkinV. A.noemail@neicon.ruФГБНУ «Медико-генетический научный центр»; ФБУН «Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского»РоссияResearch Centre for Medical Genetics; G.N. Gabrichevsky Institute of Epidemiology and MicrobiologyRussian FederationФГБНУ «Медико-генетический научный центр»РоссияResearch Centre for Medical GeneticsRussian FederationФГБУ «Российская детская клиническая больница» Минздрава РоссииРоссияRussian Pediatric Clinical HospitalRussian FederationНИИ пульмонологииРоссияPulmonology Research InstituteRussian FederationФБУН «Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского»РоссияG.N. Gabrichevsky Institute of Epidemiology and MicrobiologyRussian Federation2017180420171613745Copyright © Шмарина Г.В., Пухальская Д.А., Букина А.М., Авакян Л.В., Семыкин С.Ю., Амелина Е.Л., Красовский С.А., Усачева М.Ю., Алешкин В.А., 20172017Шмарина Г.В., Пухальская Д.А., Букина А.М., Авакян Л.В., Семыкин С.Ю., Амелина Е.Л., Красовский С.А., Усачева М.Ю., Алешкин В.А.Shmarina G.V., Pukhalskaya D.A., Bukina A.M., Avakian L.V., Semykin S.U., Amelina E.L., Krasovskiy S.A., Usacheva M.V., Alioshkin V.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.medgen-journal.ru/jour/article/view/228

Цель настоящей работы состояла в исследовании влияния аллельного полиморфизма генов TNF (транзиция G - A в промоторной области в позиции -308) и LTA (транзиция A - G в первом интроне в положении+252) на клинические параметры и маркеры воспаления у пациентов с муковисцидозом. В исследовании принимали участие 120 детей и 80 взрослых пациентов. Все пациенты находились на активном диспансерном наблюдении и регулярно (каждые 3-6 месяцев) получали антибактериальную терапию. Пациенты с генотипом LTA+252AA (низкие продуценты лимфотоксина-альфа, LTa) были существенно старше пациентов с генотипами LTA+252GG/AG (высокие продуценты LTa). В то же время пациенты двух групп не отличались по показателям функции внешнего дыхания, по частоте развития сахарного диабета и по числу умерших пациентов. Однако в группе с генотипами LTA+252GG/AG пять из шести пациентов с диабетом были моложе 14 лет. Напротив, в группе с генотипом LTA+252AA был только один (из 10) юный пациент с диабетом (р = 0,007). Исследование маркеров воспаления выявило значимое повышение уровней провоспалительных цитокинов IL-17A и IFNg в плазме пациентов с генотипами LTA+252GG/AG . У больных этой группы также отмечали выраженную тенденцию к повышению уровня IL-8. Таким образом, высокая активность системного воспалительного процесса у носителей аллеля LTA+252G отчасти объясняет более тяжелое, требующее регулярной госпитализации, течение заболевания и раннее развитие диабета в группе высоких продуцентов LT-a. Для получения достоверных данных о риске развития диабета в детском возрасте у больных с генотипами LTA+252GG/AG необходимо увеличить количество обследованных пациентов.

The aim of the study was to investigate clinical parameters and inflammatory markers in cystic fibrosis patients (CF) with TNF and LTA gene polymorphisms: a G-to-A transition in position -308 in the promoter region of the TNF gene ( rs1800629 , TNF-308 ) and a A-to-G transition at position +252 in the first intron of the LTA gene (rs909253, LTA+252 ). The study included 120 children and 80 adults with CF. All patients had regularly (every 3-6 months) attended the Russian Pediatric Clinical Hospital or Pulmonology Research Institute for routine antibiotic therapy and clinical examination. The patients with genotype LTA+252AA (low production of lymphotoxin-alpha, LTa) were significantly older than those with genotypes LTA+252GG/AG (high LTa production). In the same time the groups did not differ significantly in term their pulmonary function test results, frequency of diabetes development, or number of died patients. However, in group with genotypes LTA+252GG/AG 5 of 6 patients with diabetes were below 14 years old. In contrast, there was only patient below 14 among 10 patients with diabetes from group with genotype LTA+252AA (р = 0,007). Patients with LTA+252GG/AG genotypes had elevated plasma levels of IL-17A и IFNg. The same trend was found in relation to plasma IL-8 concentrations. In conclusion, the children with genotypes LTA+252GG/AG had more often need of hospitalization and demonstrated increased rate of diabetes development. These phenomena may be partly explained by increased grade of systemic inflammation in the carriers of LTA+252G alleles. Further investigations with prolonged observation period and increased number of participants are needed to assess the risks of early diabetes development in CF patients with LTA+252 polymorphisms.

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