Expression Analysis of Long Non-coding RNA Lnc-DC in HLA-DRB1*15:01-Negative Patients with Multiple Sclerosis: A Probable Cause for Gender Differences in Multiple Sclerosis Susceptibility?

Abstract

Multiple sclerosis is a disease that affects male and female patients differently. Several studies have been performed to explain the gender differences in MS susceptibility, but the genetic causes underlying gender differences remain unknown. The association between multiple sclerosis and the HLA-DRB1*15:01 haplotype has been confirmed to be female-specific. We hypothesized other immunological components such as lnc-DC may be gender-specific among multiple sclerosis patients, especially when MS patients are negative for the HLA-DRB1*15:01 allele. Therefore, the current study, considering the results of previous studies, aimed to evaluate the expression level of the lnc-DC gene in HLA-DRB1*15:01-negative female patients with relapsing remitting MS (RRMS). A total of 50 MS female patients and 50 female healthy controls were enrolled in this observational case-control study. HLA-DRB1*15:01, as a critical risk factor for MS, was ruled out in all patients. The peripheral blood mononuclear cells were obtained from all patients and total RNA was isolated and cDNA synthesis was carried out. The gene expression of lnc-DC was evaluated by real-time quantitative PCR. Our results have shown that lnc-DC expression level was significantly higher in total MS female patients compared with female controls (P = 0.0044). In addition, the correlation between lnc-DC with disease duration, EDSS, and age at onset did not reach a statistical significance in our study (r = 0.0336, P = 0.817; r = 0.0914, P = 0.5278 and r = 0.0743, P = 0.6083, respectively). Our results give further evidence that lnc-DC may play a gender-dependent role in MS pathogenesis.