medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2022.07.60-62medgen-2118Research ArticleКРАТКОЕ СООБЩЕНИЕBRIEF REPORTПолногеномный поиск SNPs в таргетных сайтах миРНК в 3’нетранслируемой области мРНК, связанных с индивидуальной чувствительностью к лекарствамThe genome-wide search of SNPs in 3’-UTR microRNA target sequences associated with individual drug susceptibilityКорболинаЕ. Е.KorbolinaE. .noemail@neicon.ruЕршовН. И.ErshovN. .noemail@neicon.ruРыковаЕ. Ю.RykovaE. .rykova.elena.2014@gmail.comФедеральный исследовательский центр «Институт цитологии и генетики СО РАН»РоссияFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian FederationФедеральный исследовательский центр «Институт цитологии и генетики СО РАН»; Институт химической биологии и фундаментальной медицины СО РАН; Новосибирский государственный технический университетРоссияFederal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Institute of Сhemical Biology and Fundamental Medicine of the Siberian Branch of the RAS; Novosibirsk State Technical UniversityRussian Federation2022081220222176062Copyright © Корболина Е.Е., Ершов Н.И., Рыкова Е.Ю., 20222022Корболина Е.Е., Ершов Н.И., Рыкова Е.Ю.Korbolina E..., Ershov N..., Rykova 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.medgen-journal.ru/jour/article/view/2118

Методы. Для анализа были взяты 253 аллель-асимметричных события, возникающие или усиливающиеся в 5 типах клеток человека в ответ на экзогенные соединения, включающие ряд фармакологических препаратов и 5402 eQTLs, выявленных при обработке интерфероном гамма (ИФН-γ) моноцитов периферической крови человека (PBMC). Были выбраны SNPs, локализованные в 3’UTR транскриптов, и выполнен поиск потенциальных сайтов связывания миРНК с использованием базы данных PolymiRTS. Результаты. В 5270 SNPs, проявивших себя как eQTLs, обеспечивающих реакцию PBMC на ИФН-γ, выявлены 307 событий, расположенных в предсказанных сайтах связывания миРНК, аффинность которых хотя бы к одной миРНК менялась в результате нуклеотидной замены. Среди 253 событий ASE 58 совпадали с вариациями, затрагивающими сайты связывания миРНК в 3’UTR различных мРНК. В большинстве случаев снижение экспрессии варианта соответствовало появлению сайта связывания миРНК. Заключение. Как анализ eQTL, так и поиск ASE являются эффективными инструментами выявления SNPs, расположенных в 3’UTR таргетных сайтов миРНК и связанных с индивидуальным ответом на лекарства.

The aim of this study was the identification of SNPs in 3’-UTR microRNA (miRNA) target sequences, underlining individual drug susceptibility, based on available data on eQTL and allele-specific expression (ASE) analysis. Methods and Algorithms: The search for SNPs in 3’-UTR miRNA target sites was carried out in 253 ASE events identified upon exposure of 5 human cell types to various drugs, nutrients and pollutants [1] and in 5402 eQTLs that appeared upon treatment of CD14+ monocytes with IFN-γ [2]. Data on the functional impact of SNPs on predicted miRNA sites were taken from the PolymiRTS database. Results: Of the 5402 eQTLs identified under IFN-γ treatment, 317 contained predicted miRNA binding sites affected by the nucleotide substitution. The highest enrichment in the group of 317 eQTLs was shown for the terms «cellular response to stress» (41 genes) and «immune response» (36 genes). Out of 253 ASE events, 58 coincided with the predicted SNPs in 3’-UTR miRNA target sequences. In most cases, reduced expression of the allelic variant corresponded to the appearance of a binding site for a particular miR(s). Conclusion: Both eQTL and ASE analysis are effective tools to identify SNPs located in 3’-UTR miRNA target sequences and associated with individual drug response.

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