The genome-wide search of SNPs in 3’-UTR microRNA target sequences associated with individual drug susceptibility

Abstract

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.