A genetic variant associated with multiple sclerosis inversely affects the expression of CD58 and microRNA-548ac from the same gene

摘要: Genome-wide association studies have identified more than 200 genetic variants to be associated with an increased risk of developing multiple sclerosis (MS). Still, little is known about the causal molecular mechanisms that underlie contribution disease susceptibility. In this study, we investigated role single-nucleotide polymorphism (SNP) rs1414273, which located within microRNA-548ac stem-loop sequence in first intron CD58 gene. We conducted expression quantitative trait locus (eQTL) analysis based on public RNA-sequencing and microarray data blood-derived cells 1000 subjects. Additionally, transcripts mature hsa-miR-548ac molecules were measured using real-time PCR peripheral blood samples 32 MS patients. Cell culture experiments performed evaluate efficiency Drosha-mediated processing dependent genotype determine target genes underexplored microRNA. Across different global populations sets, carriers allele showed reduced mRNA levels but levels. provide evidence SNP rs1414273 might alter Drosha cleavage activity, thereby provoking partial uncoupling gene production from shared primary transcript immune cells. Moreover, microRNA was found regulate genes, participate inflammatory processes controlling balance protein folding degradation. thus uncovered new regulatory implications MS-associated haplotype locus, remind paradoxical findings can encountered eQTLs upon aggregation. Our study illustrates a better understanding RNA events help establish functional nature variants, predispose neurological diseases.