LncRNA GAS5 and miR-137 Polymorphisms and Expression are Associated with Multiple Sclerosis Risk: Mechanistic Insights and Potential Clinical Impact

The pathogenesis of multiple sclerosis (MS) is influenced by the interaction of genetic and epigenetic mechanisms. The long noncoding RNA GAS5 acts as a competing endogenous RNA for microRNA-137 and is involved in demyelination. We investigated the association of GAS5 and miR-137 expression and their polymorphisms with MS susceptibility. One hundred and eight MS patients and 104 healthy controls were included. Expression analysis and genotyping of GAS5-rs2067079 and miR-137-rs1625579 single nucleotide polymorphisms were performed by qPCR. Serum GAS5 was upregulated, while serum miR-137 was downregulated in MS compared with the controls. Serum miR-137 was an excellent discriminator of MS patients from the controls (AUC = 0.97) and a negative independent predictor of MS in multivariate logistic analysis. Serum GAS5 expression was positively correlated with the expanded disability status scale scores in the relapsing–remitting MS patients. The rs2067079TT minor homozygote genotype was associated with an increased MS risk, while the rs1625579G minor allele was protective. rs1625579 showed an age-specific effect, while the rs2067079 affected the MS risk in gender- and age-specific manners. In MS patients, rs2067079TT was associated with a higher serum GAS5 than other genotypes, while serum miR-137 did not differ between rs1625579 genotypes. Our results suggest serum GAS5 and miR-137 as MS biomarkers, with miR-137 as a negative predictor of MS risk and GAS5 as a marker of MS severity. We propose rs2067079 and rs1625579 as novel genetic markers of MS susceptibility, and at least, rs2067079 possibly impacts the crosstalk between GAS5 and miR-137.