rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2015-6-6-18rmt-1495Research ArticleМЕТА-АНАЛИЗMETA-ANALYSISРИСК РАЗВИТИЯ ПНЕВМОНИИ И ПОЛИМОРФИЗМ ГЕНОВ TLR2 И TLR4: МЕТА-АНАЛИЗRISK FOR PNEUMONIA AND TLR2 AND TLR4 GENE POLYMORPHISMS: A META-ANALYSISСмирноваС. В.SmirnovaS. V.

Россия, 117971, Москва, ул. Губкина, д. 3

3, Gubkin St., Moscow 117971, Russia

vsmirnov64@mail.ruСальниковаЛ. Е.SalnikovaL. E.

Россия, 117971, Москва, ул. Губкина, д. 3

Россия, 107031, Москва, ул. Петровка, д. 25, стр. 2

3, Gubkin St., Moscow 117971, Russia

25, Petrovka St., Build. 2, Moscow 107031, Russia

vsmirnov64@mail.ruИнститут общей генетики им. Н. И. ВавиловаРоссияV. N. Vavilov Institute of General GeneticsRussian FederationИнститут общей генетики им. Н. И. Вавилова НИИ общей реаниматологии им. В. А. НеговскогоРоссияV. N. Vavilov Institute of General Genetics V. A. Negovsky Research Institute of General ReanimatologyRussian Federation201516012016116618Copyright © Смирнова С.В., Сальникова Л.Е., 20162016Смирнова С.В., Сальникова Л.Е.Smirnova S.V., Salnikova L.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/1495

Пневмония является одной из наиболее распространенных инфекций с высоким уровнем смертности. Полиморфизм генов толл-подобных рецепторов, относящихся к первой линии защиты иммунной системы, может вносить существенный вклад в индивидуальную вариабельность в связи с риском развития пневмонии. На сегодняшний день этот вопрос недостаточно изучен, а имеющиеся литературные данные противоречивы. Цель исследования. Мета-анализ ассоциации полиморфных вариантов генов толл-подобных рецепторов и риска развития пневмонии и сопутствующих ей инфекций. Методы. Для обнаружения возможной ассоциации риска развития пневмонии и сопутствующих инфекций с однонуклеотидными полиморфизмами (SNP) в генах TLR2 rs5743708 (2258 G>A; Arg753Gln) и TLR4 rs4986790 (896A>G; Asp299Gly) был выполнен мета-анализ. В исследование было включено 2312 (682 пациента / 1630 индивидуумов контрольной группы) и 3075 (910/2165) представителей европеоидной расы для каждого SNP соответственно. Так как частота минорных аллелей обоих полиморфных вариантов составляет менее 5%, анализ выполнен только для доминантной генетической модели. Результаты. При анализе общей группы аллель А гена TLR2 (rs5743708) показал ассоциацию с риском развития пневмонии (OR=1,90, 95% ДИ: 1,02—3,54, p=0,042), в то время как для гена TLR4 (rs4986790) ассоциации с пневмонией выявлено не было. При анализе подгрупп (дети/взрослые и внебольничная пневмония/нозокомиальная пневмония) значимые эффекты отсутствовали. Выводы. Аллель А гена TLR2 (rs5743708) может быть фактором риска восприимчивости к пневмонии. Данные результаты имеют перспективы для их использования в клинической практике, однако, в связи с высокой гетерогенностью и недостаточными размерами выборок, требуется подтверждение этих результатов в дальнейших исследованиях.

Pneumonia is one of the most common infections with high mortality rates. The gene polymorphism of Toll-like receptors that belong to the first line of defense of the immune system can make a considerable contribution to individual variability due to the risk of pneumonia. Today this issue has not been adequately explored and the data available in the literature are conflicting.

Objective

Objective: to carry out a meta-analysis of the association between Toll-like receptor gene polymorphic variants and the risk of pneumonias and its coinfections.

Methods

Methods. A meta-analysis was carried out to detect a possible association of the risk of pneumonia and coinfections with single nucleotide polymorphisms (SNP) in the TLR2 (rs5743708 (2258 G>A; Arg753Gln) and TLR4 (rs4986790 (896A>G; Asp299Gly) genes. The investigation enrolled 2312 (682 patients/1630 control individuals) and 3075 (910/2165) Caucasians for each SNP, respectively. As the rate of minor alleles of both polymorphic variants was less than 5%; the analysis was made only for a dominant genetic model.

Results

Results. Analysis of the study group showed that the A allele of TLR2 rs5743708 was associated with the risk of pneumonia (OR = 1.90; 95% CI: 1.02—3.54; P=0.042) while TLR4 rs4986790 was not associated with pneumonia. Analysis of subgroups (children/adults and community-acquired/nosocomial pneumonia) revealed no significant effects.

Conclusion

Conclusion. The A allele of TLR2 rs5743708 may be a risk factor for susceptibility to pneumonia. These results have promises for their clinical application; however, due to the high heterogeneity and insufficient sizes of samples, these results need to be confirmed by further investigations.

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