Association study of promoter polymorphisms of interferon alpha and beta receptor subunit 1 (IFNAR1) gene and therapeutic response to interferon-beta in patients with multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease described by inflammatory neuronal losses and resultant failures. The disease could abate by interferon-beta (IFN-β) therapy in MS patients. However, the drug response productivity is changeable between patients, and the accurate mechanism of action of the IFN-β is not obvious. The present study aims to investigate the role of interferon alpha and beta receptor subunit 1 (IFNAR1) promoter polymorphisms towards IFN-β treatment response in MS patients. Methods: The subjects herein were separated into either responder (n = 57) or non-responder (n = 43) groups according to IFN-β treatment and Expanded Disability Status Scale score. The Sanger sequencing method was used for genotyping. Results: Among nearly 64 Single Nucleotide Polymorphisms (SNPs), we found a significant association between the rs2850015 polymorphism and the responders and non-responders to IFN-β treatment in the recessive model of inheritance (P = 0.02). The results also revealed a significant change in the two groups of responders and non-responders to the treatment for rs36158718 as an Insertion/Deletion (INDEL) (P = 0.02). Moreover, bioinformatic analyses predicted a remarkable role for both rs2850015 and rs36158718 related to the changes of binding affinity of transcription factors and alterations in their alleles. Conclusion: The present study results suggest that the genetic heterogeneity in the promoter region of IFNAR1 could affect the response to IFN-β. However, further studies with a larger sample size are needed to further demonstrate this relationship.