Expression Analysis of GSTT1-AS1 Long Noncoding RNA and Its Coding Target Gene, TNFA, in Iranian Multiple Sclerosis Patients

Introduction: Multiple sclerosis (MS) is a complex autoimmune disorder and the most common cause of nontraumatic disability in young people. Long noncoding RNAs (lncRNAs) have been recently reported to participate in immune responses adjustment. Likewise, epigenetic regulation of gene expression is substantial in immunopathology of various autoimmune diseases.Methods: The aim of this experimental study was to investigate the expression levels of GSTT1-AS1 lncRNA and TNFA gene, as its target, in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls through SYBR Green Quantitative Real-Time PCR.Results: We found a significant down-regulation of GSTT1-AS1 expression in MS patients, total female MS patients and female patients aged > 40, compared with corresponding control group (r=-0.15, P=0.032; r=-0.4, P=0.045, and r=-0.47, P=0.0005 respectively). TNFA showed an increased expression but, however, did not reach a significant level (r=-0.26, P=0.303). Moreover, Spearman correlation analysis between GSTT1-AS1 relative expression and age at onset as well as TNFA expression level displayed significant correlation in patients (r=0.313, P=0.027; r=0.204, P=0.041, respectively). A moderate correlation between TNFA and Expanded Disability Status Scale (EDSS) in MS patients was observed (r=-0.28, P=0.049).Conclusion: This study implicates the dysregulation of GSTT1-AS1 lncRNA and TNFA gene in MS patients. Considering the epigenetic role of GSTT1-AS1 in methylation of genomic areas such as TNFA locus, we can suggest an imbalance in this lncRNA and its target might contribute to the pathophysiology of MS. Further studies could shed light on the underlying mechanisms participating in the regulation of immune responses.

Keywords:

Long Noncoding RNA , GSTT1-AS1 , TNFA , Multiple Sclerosis , Gene Expression.