{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:21:37Z","timestamp":1782793297708,"version":"3.54.5"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The main carrier protein of vitamin D and its metabolites in plasma is vitamin D binding protein (VDBP) or group-specific component (Gc). Two single nucleotide polymorphisms, rs7041, and rs4588 in the <jats:italic>GC<\/jats:italic> gene result in three major VDBP\/Gc genotypes, <jats:italic>GC1F<\/jats:italic> (c.1296T, c.1307C), <jats:italic>GC1S<\/jats:italic> (c.1296G, c.1307C), <jats:italic>GC2<\/jats:italic> (c.1296T, c.1307A), and phenotypes, Gc1F (p.432Asp, p.436Thr), Gc1S (p.432Glu, p.436Thr), and Gc2 (p.432Asp, p.436Lys). This study investigated frequencies of <jats:italic>GC<\/jats:italic> genotypes and phenotypes in Kuwaiti multiple sclerosis (MS) patients and healthy controls, and their associations with serum levels of 25 hydroxyvitamin D [25(OH)vitamin D] and VDBP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genomic DNA was isolated from blood samples of drug-na\u00efve MS patients (<jats:italic>N<\/jats:italic>\u202f=\u202f151) and controls (<jats:italic>N<\/jats:italic>\u202f=\u202f127). DNA regions covering the targeted mutations were amplified by PCR, sequenced by the Sanger method, and analyzed to determine <jats:italic>GC<\/jats:italic> genotypes and phenotypes. Serum 25(OH)vitamin D and VDBP levels were measured by enzyme immunoassay. SPSS used for statistical analyses. Differences between independent and related groups tested by Mann\u2013Whitney <jats:italic>U<\/jats:italic> and Wilcoxon signed-rank tests respectively, Genotype and phenotype frequencies were calculated; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05 considered significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study detected four Gc genotypes\/phenotypes, namely <jats:italic>GC1F<\/jats:italic>\/Gc1F (c.1296T, c.1307C\/p.432Asp, p.436Thr), <jats:italic>GC1S<\/jats:italic>\/Gc1S (c.1296G, c.1307C\/p.432Glu, p.436Thr), <jats:italic>GC2<\/jats:italic>\/Gc2 (c.1296T, c.1307A\/p.432Asp, p.436Lys), and <jats:italic>GC3<\/jats:italic>\/Gc3 (c.1296G; c.1307A\/p.432Glu, p.436Lys) in both subjects. The frequencies of <jats:italic>GC3<\/jats:italic> genotype (control: 5.51%; patient: 28.48%) and Gc3-containing phenotypic groups (Gc1S\/Gc3\u202f+\u202fGc2\/Gc3\u202f+\u202fGc3\/Gc3) were significantly higher in patients. Moreover, frequencies of <jats:italic>GC1F<\/jats:italic> genotype (control: 27.17%; patients: 5.30%) and Gc1F-containing phenotypic groups (Gc1F\/Gc1F\u202f+\u202fGc1S\/Gc1F\u202f+\u202fGc2\/Gc1F) were higher in controls. Vitamin D levels were deficient in both groups. However, VDBP concentrations were significantly low in MS patients only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The VDBP\/GC genotypes and phenotypes are associated with MS. Common genotype <jats:italic>GC1F<\/jats:italic> might be protective, and <jats:italic>GC3<\/jats:italic>, the novel variant found in MS patients appeared to be pathogenetic. Hypovitaminosis-D is prevalent in MS patients and controls.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1455779","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T05:10:57Z","timestamp":1738905057000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Potential pathogenic and protective genotypes and phenotypes of vitamin D binding protein in multiple sclerosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Suhail","family":"Al-Shammri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Chattopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu Salim","family":"Mustafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1093\/brain\/awp033","article-title":"Immunomodulatory effects of vitamin D in multiple sclerosis","volume":"132","author":"Correale","year":"2009","journal-title":"Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.ncl.2016.06.016","article-title":"Epidemiology of multiple sclerosis","volume":"34","author":"Howard","year":"2016","journal-title":"Neurol Clin"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/0022-510X(90)90024-H","article-title":"Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians","volume":"100","author":"Al-Din","year":"1990","journal-title":"J Neurol 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