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多发性硬化症患者的表达及单核苷酸变异影响对β-干扰素治疗的反应。

Expression and Single Nucleotide Variants in Multiple Sclerosis Patients Affect the Response to Interferon Beta Therapy.

作者信息

Fakhr Fatemeh, Shaygannejad Vahid, Khorrami Mehdi, Saberi Leila, Mirmosayyeb Omid, Sadeghi Erfan, Kheirollahi Majid

机构信息

Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Neurosciences Research Center, Alzahra Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Glob Med Genet. 2023 Jul 10;10(3):164-171. doi: 10.1055/s-0043-1771001. eCollection 2023 Sep.

Abstract

Interferon (IFN)-β is the first-line disease management choice in multiple sclerosis (MS) with profound effects; however, in up to 50% of patients, clinical response does not occur. Ascertaining the responding state, need a long-term clinical follow-up, and this may lead to delay in use of other effective medications. IFN-induced cascade and its regulation is considered to play a major role in MS. Adenosine deaminase, RNA-specific (ADAR) dysregulation is important to IFN signaling pathway as an activity suppressor. Hence, we investigated the expression of and its single nucleotide variants of rs2229857 association with response to IFN-β in relapsing-remitting MS patients. mRNA levels and genotyping of rs2229857 in 167 MS patients were investigated via SYBR Green real-time (RT)-quantitative polymerase chain reaction and high-resolution melting RT PCR, respectively. The allele-A in rs2229857 and higher expression of were associated with poor response to IFN-β. Two response groups were significantly different in terms of annualized relapse rate, first symptoms, first extended disability status scale (EDSS), current EDSS, and the MS severity score. According to this study's findings, assessment of transcript levels and also variants in ADAR may be useful in identifying patients' response to IFN-β before starting treatment. Further investigations are needed to determine the potency of ADAR to be a predictive biomarker in drug responsiveness.

摘要

干扰素(IFN)-β是多发性硬化症(MS)一线疾病管理的选择,具有深远影响;然而,高达50%的患者未出现临床反应。确定反应状态需要长期临床随访,这可能导致其他有效药物使用的延迟。IFN诱导的级联反应及其调节被认为在MS中起主要作用。腺苷脱氨酶,RNA特异性(ADAR)失调作为一种活性抑制剂对IFN信号通路很重要。因此,我们研究了复发缓解型MS患者中ADAR的表达及其单核苷酸变体rs2229857与IFN-β反应的相关性。分别通过SYBR Green实时(RT)定量聚合酶链反应和高分辨率熔解RT PCR研究了167例MS患者中rs2229857的mRNA水平和基因分型。rs2229857中的等位基因A和ADAR的高表达与对IFN-β的不良反应相关。两个反应组在年化复发率、首发症状、首次扩展残疾状态量表(EDSS)、当前EDSS和MS严重程度评分方面存在显著差异。根据本研究结果,在开始治疗前评估ADAR的转录水平和变体可能有助于识别患者对IFN-β的反应。需要进一步研究以确定ADAR作为药物反应预测生物标志物的效力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2795/10370467/b86de597ef2a/10-1055-s-0043-1771001-i2300031-1.jpg

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