Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmide Blvd, 6517838678, Hamadan, Iran.
Department of Neurology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Mol Biol Rep. 2021 Aug;48(8):6007-6013. doi: 10.1007/s11033-021-06602-8. Epub 2021 Jul 30.
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.
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.
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.
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.
多发性硬化症（MS）是一种自身免疫性疾病，其特征是炎症性神经元丧失和由此导致的功能障碍。干扰素-β（IFN-β）治疗可缓解 MS 患者的病情。然而，药物反应的有效性在患者之间存在差异，且 IFN-β 的作用机制尚不清楚。本研究旨在探讨干扰素-α和β受体亚单位 1（IFNAR1）启动子多态性对 MS 患者 IFN-β 治疗反应的作用。
根据 IFN-β 治疗和扩展残疾状况量表评分，将研究对象分为应答者（n=57）和非应答者（n=43）组。采用 Sanger 测序法进行基因分型。
在近 64 个单核苷酸多态性（SNP）中，我们发现 rs2850015 多态性与 IFN-β 治疗的应答者和非应答者之间存在显著关联，在隐性遗传模型中（P=0.02）。结果还显示，rs36158718 作为插入/缺失（INDEL）在应答者和非应答者两组之间的治疗效果存在显著变化（P=0.02）。此外，生物信息学分析预测 rs2850015 和 rs36158718 都与转录因子结合亲和力的变化和等位基因的改变有关。
本研究结果表明，IFNAR1 启动子区的遗传异质性可能影响 IFN-β 的治疗反应。然而，需要进一步的研究来验证这种关系。
