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Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis : A presymptomatic case–control study

Grut, Viktor ; Biström, Martin ; Salzer, Jonatan ; Stridh, Pernilla ; Lindam, Anna ; Alonso-Magdalena, Lucia LU ; Andersen, Oluf ; Jons, Daniel ; Gunnarsson, Martin and Vrethem, Magnus , et al. (2022) In European Journal of Neurology 29(8). p.2335-2342
Abstract

Background and purpose: High levels of 25-hydroxyvitamin D3 (25[OH]D3) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS. Methods: A nested case–control study was performed with presymptomatic serum samples identified... (More)

Background and purpose: High levels of 25-hydroxyvitamin D3 (25[OH]D3) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS. Methods: A nested case–control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3/DBP) × 103. MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15–0.91, p for trend across quintiles = 0.04). At age 30–39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15–0.85, p for trend = 0.02). Conclusions: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
case–control studies, multiple sclerosis, vitamin D, vitamin D-binding protein
in
European Journal of Neurology
volume
29
issue
8
pages
8 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:35582958
  • scopus:85131168703
ISSN
1351-5101
DOI
10.1111/ene.15407
language
English
LU publication?
yes
additional info
Funding Information: This study was supported by the Swedish Research Council, grant 2015‐02419; by the Visare Norr Fund, Northern County Councils' Regional Federation, grant 940405; by the Research and Development Unit, Region Jämtland Härjedalen, grant JLL‐939768; and by NEURO Sweden. P.St. received funding from Margaretha af Ugglas stiftelse, the Swedish Neuro Foundation, and the MS Research fund. The Swedish MS registry is gratefully acknowledged. We would like to thank the participants in the cohorts, as well as all staff in the biobanks involved in collecting the samples. We also appreciate the assistance provided by the staff at the chromatography unit at Clinical Chemistry, Laboratory Medicine, Umeå University Hospital for the analysis of 25(OH)D, and Parviz Behnam Motlagh for technical assistance with the DPB analysis. 3 Funding Information: This study was supported by the Swedish Research Council, grant 2015-02419; by the Visare Norr Fund, Northern County Councils' Regional Federation, grant 940405; by the Research and Development Unit, Region Jämtland Härjedalen, grant JLL-939768; and by NEURO Sweden. P.St. received funding from Margaretha af Ugglas stiftelse, the Swedish Neuro Foundation, and the MS Research fund. The Swedish MS registry is gratefully acknowledged. We would like to thank the participants in the cohorts, as well as all staff in the biobanks involved in collecting the samples. We also appreciate the assistance provided by the staff at the chromatography unit at Clinical Chemistry, Laboratory Medicine, Umeå University Hospital for the analysis of 25(OH)D3, and Parviz Behnam Motlagh for technical assistance with the DPB analysis. Publisher Copyright: © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
id
4d874422-cd7d-42ab-8318-974b3ad56db2
date added to LUP
2022-12-30 11:16:44
date last changed
2024-07-08 07:22:54
@article{4d874422-cd7d-42ab-8318-974b3ad56db2,
  abstract     = {{<p>Background and purpose: High levels of 25-hydroxyvitamin D<sub>3</sub> (25[OH]D<sub>3</sub>) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D<sub>3</sub> is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D<sub>3</sub> can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D<sub>3</sub> or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D<sub>3</sub> and DBP as risk factors for MS. Methods: A nested case–control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D<sub>3</sub> was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D<sub>3</sub> was approximated as free vitamin D<sub>3</sub> index: (25[OH]D<sub>3</sub>/DBP) × 10<sup>3</sup>. MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: Serum samples from 660 pairs of matched cases and controls were included. At &lt;20 years of age, high levels of free vitamin D<sub>3</sub> index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15–0.91, p for trend across quintiles = 0.04). At age 30–39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15–0.85, p for trend = 0.02). Conclusions: These findings support the hypothesis that high levels of free 25(OH)D<sub>3</sub> at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.</p>}},
  author       = {{Grut, Viktor and Biström, Martin and Salzer, Jonatan and Stridh, Pernilla and Lindam, Anna and Alonso-Magdalena, Lucia and Andersen, Oluf and Jons, Daniel and Gunnarsson, Martin and Vrethem, Magnus and Hultdin, Johan and Sundström, Peter}},
  issn         = {{1351-5101}},
  keywords     = {{case–control studies; multiple sclerosis; vitamin D; vitamin D-binding protein}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2335--2342}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Neurology}},
  title        = {{Free vitamin D<sub>3</sub> index and vitamin D-binding protein in multiple sclerosis : A presymptomatic case–control study}},
  url          = {{http://dx.doi.org/10.1111/ene.15407}},
  doi          = {{10.1111/ene.15407}},
  volume       = {{29}},
  year         = {{2022}},
}