Vitamin D affects the risk of disease activity in multiple sclerosis.

MULTIPLE SCLEROSIS NEUROIMMUNOLOGY

Journal

Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R

Informations de publication

Date de publication:
14 Jul 2024
Historique:
received: 16 04 2024
accepted: 19 06 2024
medline: 15 7 2024
pubmed: 15 7 2024
entrez: 14 7 2024
Statut: aheadofprint

Résumé

Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity. 230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality. Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041). VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.

Sections du résumé

BACKGROUND BACKGROUND
Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.
METHODS METHODS
230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.
RESULTS RESULTS
Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).
CONCLUSIONS CONCLUSIONS
VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.

Identifiants

pubmed: 39004505
pii: jnnp-2024-334062
doi: 10.1136/jnnp-2024-334062
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Antonino Giordano (A)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Università Vita Salute San Raffaele, Milano, Italy.
Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Ferdinando Clarelli (F)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Béatrice Pignolet (B)

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, Toulouse, France.
Neurosciences Department, Toulouse University Hospital, Toulouse, France.

Elisabetta Mascia (E)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Melissa Sorosina (M)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Kaalindi Misra (K)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Laura Ferrè (L)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Florence Bucciarelli (F)

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, Toulouse, France.

Ali Manouchehrinia (A)

Neuroimmunology Unit, Karolinska Institute, Stockholm, Sweden.

Lucia Moiola (L)

Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Vittorio Martinelli (V)

Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Maria A Rocca (MA)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Università Vita Salute San Raffaele, Milano, Italy.
Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Roland Liblau (R)

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, Toulouse, France.
Department of Immunology, Toulouse University Hospitals, Toulouse, France.

Massimo Filippi (M)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Università Vita Salute San Raffaele, Milano, Italy.
Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Federica Esposito (F)

Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy esposito.federica@hsr.it.
Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Classifications MeSH