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

• Published in: Molecular biology reports Vol. 48; no. 8; pp. 6007 - 6013
• Main Authors: Hajian, Samin, Mazdeh, Mehrdokht, Nouri, Fatemeh, Roshanaei, Ghodratollah, Soleimani, Meysam
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2021; Springer Nature B.V
• Subjects: Adult; Alleles; Animal Anatomy; Animal Biochemistry; Autoimmune diseases; bioinformatics; Biomarkers, Pharmacological; Biomedical and Life Sciences; drugs; Female; genetic heterogeneity; Genome-Wide Association Study - methods; Genotype; Genotyping; Heredity; Histology; Humans; Indonesia - epidemiology; Insertion; Interferon; Interferon-alpha - genetics; Interferon-alpha - therapeutic use; interferon-beta; Interferon-beta - genetics; Interferon-beta - therapeutic use; Life Sciences; Male; mechanism of action; Middle Aged; molecular biology; Morphology; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; neurons; Original Article; Patients; Polymorphism, Single Nucleotide - genetics; promoter regions; Promoter Regions, Genetic - genetics; Receptor, Interferon alpha-beta - genetics; Receptor, Interferon alpha-beta - metabolism; Receptors, Interferon - genetics; sample size; sclerosis; Single-nucleotide polymorphism; therapeutics; Transcription factors; β-Interferon; Indonesia; Multiple sclerosis; IFN-β; SNP; IFNAR1; INDEL
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-021-06602-8

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.