{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:01:13Z","timestamp":1780290073799,"version":"3.54.0"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple Sclerosis (MS) is a neuroinflammatory disorder in which genetic and environmental factors contribute to disease onset. Evidence implicates the inflammasome pathway in MS pathophysiology. However, the interaction between inflammasome-related genetic variants and 25-OH-vitamin D3 (25(OH)D3) levels remains unclear. 105 MS patients and 109 healthy controls were enrolled. Genotyping of NLRP3 (rs10754558, rs3806265) and NLRC4 (rs479333) polymorphisms was performed using real-time PCR. Serum 25(OH)D3 levels were measured by high-performance liquid chromatography. Clinical severity was assessed using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS), annualized relapse rate (ARR), and age at onset. MS patients showed significantly lower serum 25(OH)D3 levels than controls. Genotype distributions did not differ significantly under an additive model; however, the NLRP3 rs10754558 GG genotype was more frequent in MS patients under a recessive model and was significantly associated with disease status after adjustment for sex. Subjects carrying the GG genotype also had significantly lower serum 25(OH)D3 levels than CC\/CG carriers, independently of sex. No significant associations were observed for NLRP3 rs3806265 or NLRC4 rs479333, and none of the investigated variants was associated with EDSS, MSSS, ARR, or age at onset. The NLRP3 rs10754558 polymorphism may be associated with MS susceptibility and reduced circulating vitamin D levels, suggesting a potential link between inflammasome-related genetic variability and immunometabolic regulation in MS.<\/jats:p>","DOI":"10.3390\/ijms27114681","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"4681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammasome Gene Polymorphisms (NLRP3 and NLRC4) and Vitamin D Status in Patients with Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-8066","authenticated-orcid":false,"given":"Concetta","family":"Scazzone","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Agnello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina Maria","family":"Gambino","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0611-9363","authenticated-orcid":false,"given":"Chiara","family":"Bellia","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-4323","authenticated-orcid":false,"given":"Giuseppe","family":"Salemi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Masucci","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Novara","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-9041","authenticated-orcid":false,"given":"Marcello","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Clinical Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University Hospital Paolo Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: The 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1474-4422(14)70305-9","article-title":"Role of the innate and adaptive immune responses in the course of multiple sclerosis","volume":"14","author":"Hemmer","year":"2015","journal-title":"Lancet 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