Role of NR3C1 and GAS5 genes polymorphisms in multiple sclerosis

Introduction: Multiple sclerosis (MS) as a progressive chronic disease of the central nervous system (CNS) is characterized by demyelination and axonal loss. Results of genetic studies and clinical trials have proved a key role for the immune system in the pathogenesis of MS. Glucocorticoids (GR) are regarded as potent therapeutic compounds for autoimmune and inflammatory diseases which act through their receptors encoded by Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene. Meanwhile, the long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) interacts with GR through binding to the DNA-binding domain (DBD) region and reduces GR transcriptional activity. Methods: The purpose of our study was to evaluate the association between MS and polymorphisms within NR3C1 (rs6189/6190, rs56149945, rs41423247) and GAS5 (rs55829688) genes in 300 relapsing-remitting MS patients and 300 healthy subjects. Results: We demonstrated significant differences in distribution of genotype, allele and haplotype frequencies of rs6189, rs41423247 and rs55829688 between the study groups. Conclusion: Our data may suggest that rs6189, rs41423247 and rs55829688 are associated with the increased risk of MS development. Future studies are needed to verify our results in larger sample sizes and elaborate the underlying mechanisms for contribution of these variants in MS disease.