Background:
Multiple Sclerosis (MS) is an inflammatory and demyelinating
disease of the central nervous system, and genetic factors play an important role in its susceptibility.
The expressions of many inflammatory genes implicated in MS are regulated
by microRNA (miRNAs), whose function is to suppress the translation by pairing with
miRNA Recognition Elements (MREs) present in the 3' untranslated region (3'UTR) of
target mRNA. Recently, it has been shown that the Single Nucleotide Polymorphism
(SNPs) present within the 3'UTR of mRNAs can affect the miRNA-mediated gene regulation
and susceptibility to a variety of human diseases.
Objective:
The aim of this study was to analyze the SNPs within the 3'UTR of miRNA inflammatory
target genes related to multiple sclerosis.
Methods:
By DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases,
3'UTR genetic variants were identified in all inflammatory genes associated with MS. Also,
miRNA's target prediction databases were used for predicting the miRNA binding sites.
Results:
We identified 125 SNPs with MAF>0.05 located in the binding site of the miRNA
of 35 genes among 59 inflammatory genes related to MS. Bioinformatics analysis
predicted 62 MRE-modulating SNPs and 59 MRE-creating SNPs in the 3'UTR of MSimplicated
inflammatory genes. These candidate SNPs within miRNA binding sites of inflammatory
genes can alter the miRNAs binding, and consequently lead to the mRNA
gene regulation.
Conclusion:
Therefore, these miRNA and MRE-SNPs may play important roles in personalized
medicine of MS, and hence, they would be valuable for further functional verification
investigations.