~20-22-nucleotide-long non-coding RNAs which regulate target mRNA expression post-transcriptionally through mRNA degradation or translation inhibition (6). miRNAs serve essential roles in the immune system in the development of innate and adaptive immunity and for proper immune func- tion (7). miR-1

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. It was previously demonstrated that miR-155 and miR-146a served a vital role in the pathophysiology of MS, and single nucleotide polymorphisms in miR-155 and miR-146a were found to be associated with the susceptibility to different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type I diabetes. The aim of the present study was to analyze the association between susceptibility to MS and two genetic polymorphisms (miR-155 rs767649 A>T and miR-146a rs57095329 A>G) in a cohort of Egyptian patients. The presence of the two polymorphisms were analyzed in 114 patients with MS and 152 healthy controls using quantitative PCR. The present study demonstrated for the first time that: The TT genotype and T allele in miR-155 (rs767649 A>T) polymorphism were associated with an increased risk of MS; the miR-146a (rs57095329 A>G) mutated G allele conferred protection against the development of MS in all genetic models; miR-155 rs767649 A>T was a risk associated polymorphism of MS in females, but not in males; and miR-155 rs767649 AT/TT and miR-146a rs57095329 GG genotypes showed significantly higher distributions among patients with higher Expanded Disability Status Scale scores and secondary progressive MS subgroups. Therefore, miR-155 rs767649 polymorphism may confer susceptibility to MS, whereas miR-146a rs57095329 may be protective against MS in an Egyptian cohort. Introduction Multiple sclerosis (MS) is a non-fatal long-lasting autoimmune disease characterized by chronic inflammation and demyelinating neurodegeneration of the central nervous system (CNS) (1). There are three primary clinical subtypes of MS; ~80% are diagnosed with relapsing-remitting MS (RRMS), with secondary progressive MS (SPMS) developing in the following decades, whereas in a smaller group of patients (~20%) MS begins with a primary progressive phase (PPMS) (2). The etiology of MS remains unclear; however, several studies have shown that both genetic and environmental factors influence susceptibility to MS (3‐5). MicroRNAs (miRNAs/miRs) constitute a group of ~20-22-nucleotide-long non-coding RNAs which regulate target mRNA expression post-transcriptionally through mRNA degradation or translation inhibition (6). miRNAs serve essential roles in the immune system in the development of innate and adaptive immunity and for proper immune function (7). miR-155 regulates the innate and adaptive immune responses in response to infection (8) However, miR-155 dysregulation via overexpression is associated with various inflammatory disorders (9,10). miR-146a is a negative regulator of immune and inflammatory responses (11). miR‐155 and miR-146a are associated with the pathogenesis of several autoimmune diseases (6,12), including MS in humans and in experimental autoimmune encephalomyelitis (EAE) lesions in mice, suggesting that miR-155 and miR-146a may be involved in the pathophysiology of MS (10,13). Single nucleotide polymorphisms (SNPs) are single nucleotide variations that occur at a unique site in the DNA (14). These changes in the DNA sequence can affect the susceptibility to different diseases, including autoimmune diseases (15). SNPs in miR-155 rs767649 and miR-146a rs57095329 are associated with the development of immune-system dysfunctions (16,17). Notably, the selected SNPs (miR-155 rs767649 and miR-146a rs57095329) are located in the regulatory regions of these miRNAs and may thus affect their expression levels (16-21). Given the regulatory role of miR-155 and miR-146a in the immune response in MS and the possible effect of the miR-155 rs767649 and miR-146a rs57095329 SNPs on their Relationship between miR‐155 and miR‐146a polymorphisms and susceptibility to multiple sclerosis in an Egyptian cohort MARWA AHMED ALI1, OLFAT GAMIL SHAKER2, HANAA MOHAMED EID3, EMAN ELSAYED MAHMOUD4, EMAN MAHMOUD EZZAT5 and SYLVANA NADY GABER3 1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, Fayoum 63514; 2Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo 11562; Departments of 3Medical Microbiology and Immunology, 4Clinical and Chemical Pathology and 5Internal Medicine, Faculty of Medicine, Fayoum University, Fayoum 63514, Egypt Received July 15, 2019; Accepted December 13, 2019 DOI: 10.3892/br.2020.1286 Correspondence to: Dr Marwa Ahmed Ali, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Fayoum University, 32 Zaid Bin Haritha Street, Al Mashtal,