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Interferon-\u03b3 (IFN-\u03b3) plays a dual role in MS pathogenesis. MicroRNAs (miRNAs) have emerged as potential diagnostic biomarkers. This study examined the effect of relative expression of hsa-miR-24-3p and hsa-miR-181d-3p, plasma IFN-\u03b3 levels, and the <jats:italic>IFNG<\/jats:italic> rs2069727 T\/C variant on MS risk, evaluating their interrelationships and diagnostic potential. This case\u2013control study comprised two overlapping groups\u2014a genetic polymorphism group (330 RRMS, 330 healthy controls (HCs)) and a miRNA group (25 glatiramer acetate (GA)-treated RRMS patients, 25 treatment-na\u00efve RRMS patients, and 25 HCs)- collected at the Ankara Bilkent City Hospital Neurology Polyclinic. The <jats:italic>IFNG<\/jats:italic> rs2069727 T\/C variant did not display a statistically significant disparity between RRMS patients and HCs. Significantly elevated hsa-miR-24-3p and hsa-miR-181d-3p relative expression levels were observed in GA-treated and treatment-na\u00efve RRMS patients compared to HCs. Conversely, age-adjusted plasma IFN-\u03b3 concentrations were markedly lower in GA-treated and treatment-na\u00efve RRMS patients versus HCs. Individuals with low plasma IFN-\u03b3 levels (\u2264\u20091.311\u00a0pg\/mL) demonstrated significantly elevated hsa-miR-24-3p relative expression compared to the high IFN-\u03b3 group (&gt;\u20091.311\u00a0pg\/mL). Conversely, subjects with low hsa-miR-181d-3p levels (\u2264\u20092.90) exhibited significantly higher plasma IFN-\u03b3 concentrations relative to those with high hsa-miR-181d-3p levels (&gt;\u20092.90). In the GA-treated group, EDSS negatively correlated with age-adjusted plasma IFN-\u03b3. This study identified age-adjusted plasma IFN-\u03b3, hsa-miR-24-3p, and hsa-miR-181d-3p expression as potential blood-based biomarkers for RRMS diagnosis and analyzed them alongside disability scores. The miRNAs in this study can be further evaluated as prospective therapeutic targets.<\/jats:p>","DOI":"10.1007\/s12035-025-05027-9","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:20:50Z","timestamp":1748866850000},"page":"12865-12882","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding the Potential Impact of Plasma hsa-miR-24-3p and hsa-miR-181 d-3p Expression, Plasma IFN-\u03b3 Levels, and IFNG rs2069727 T\/C Genetic Variant on Multiple Sclerosis Risk and Glatiramer Acetate Treatment"],"prefix":"10.1007","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-3502","authenticated-orcid":false,"given":"Mekselina","family":"Kalmaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6469-5185","authenticated-orcid":false,"given":"Semra","family":"Mungan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1536-6123","authenticated-orcid":false,"given":"Birsen Can","family":"Demird\u00f6\u011fen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"issue":"11","key":"5027_CR1","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1212\/WNL.0b013e3182872855","volume":"80","author":"I Kister","year":"2013","unstructured":"Kister I, Chamot E, Salter AR, Cutter GR, Bacon TE, Herbert J (2013) Disability in multiple sclerosis: A reference for patients and clinicians. 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Approval of the study was obtained from the hospital ethics committee (date: May 26, 2021, decision no: E1-21\u20131805). Written informed consent was obtained from all participants. The study was conducted in accordance with the principles of the Declaration of Helsinki. The authors affirm that all human research participants provided informed consent for the publication of their clinical and demographic data anonymously.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval, Consent to Participate and Consent to Publish"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}