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FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

ABSTRACT: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility.

SUBMITTER: Scazzone C

PROVIDER: S-EPMC8066599 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

Scazzone Concetta C Agnello Luisa L Lo Sasso Bruna B Salemi Giuseppe G Gambino Caterina Maria CM Ragonese Paolo P Candore Giuseppina G Ciaccio Anna Maria AM Giglio Rosaria Vincenza RV Bivona Giulia G Vidali Matteo M Ciaccio Marcello M

Brain sciences 20210325 4

<h4>Background</h4>Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D<sub>3</sub>. The aim of this re ...[more]

PMID: 33806248

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Project description:ObjectiveLow vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.MethodsAn open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.ResultsForty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.ConclusionsHigh-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.Classification of evidenceThis trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes.

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FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

Publications

FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

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