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

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 ADAR 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 ADAR 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.

Keywords

multiple sclerosis / interferon-β / ADAR / rs2229857

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