RT Journal Article
SR Electronic
T1 Vitamin D affects the risk of disease activity in multiple sclerosis
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP jnnp-2024-334062
DO 10.1136/jnnp-2024-334062
A1 Giordano, Antonino
A1 Clarelli, Ferdinando
A1 Pignolet, Béatrice
A1 Mascia, Elisabetta
A1 Sorosina, Melissa
A1 Misra, Kaalindi
A1 Ferrè, Laura
A1 Bucciarelli, Florence
A1 Manouchehrinia, Ali
A1 Moiola, Lucia
A1 Martinelli, Vittorio
A1 Rocca, Maria A
A1 Liblau, Roland
A1 Filippi, Massimo
A1 Esposito, Federica
YR 2024
UL http://jnnp.bmj.com/content/early/2024/07/13/jnnp-2024-334062.abstract
AB 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 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 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 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.Data are available on reasonable request. Anonymized data of the analyses presented in this study are available upon reasonable request from the corresponding author.