Original Article
Candice Dunn, Julia O’Mahony, Heather Hanwell, Eluen Ann Yeh, Ruth Ann Marrie, Amit Bar-Or, Brenda Banwell
Neurology
Abstract
Objective: To determine whether HLA-DRB1*15 status, 25-hydroxyvitamin D (25(OH)D) levels measured at baseline, and skin tone are associated with MS outcome in children with acquired demyelinating syndromes (ADS).
Background: Multiple Sclerosis (MS) risk varies by race, vitamin D status, HLA-DRB1*15 genotype and geographic place of residence during childhood. Place of residence can affect ultraviolet radiation exposure, and consequently influence dermal pigmentation.
Design/Methods: 259 children with incident ADS were enrolled in a multi-site prospective study in Toronto and Philadelphia (43°–51° latitude). Non-sun exposed upper inner arm melanin content was measured using the DSM II ColorMeter device. 25(OH)D concentrations were measured in serum obtained within 60 days of symptom onset and compared to lab-reported normative values. Vitamin D insufficiency was defined as [25(OH)D] less than 75 nmol/l (30 ng/dl). HLA-DRB1*15 alleles were quantified using allele-specific PCR amplification. Statistical analysis was performed using Spearman correlation models and Wilcoxon or Kruskal-Wallis tests as appropriate.
Results: 68 children were diagnosed with MS, 191 remained monophasic (monoADS). 45.5% of MS children were HLA-DRB1*15 positive compared to 29.9% of monoADS children (p=0.03). Additionally, MS children had lower 25(OH)D levels (mean=45.4, SD=22.7) than monoADS children (mean=61.9, SD=29.2; p<0.0001) at baseline. Non-sun exposed skin tone measured in the upper inner arm did not differ between children diagnosed with MS (melanin index, mean=46.4, SD=12.3) and monoADS (mean=43.5, SD=8.1; p=0.61). Interestingly, 25(OH)D levels correlated with upper inner arm melanin index in the MS group (rho= −0.42, p=0.02), but not in children with monoADS (rho= −0.11, p=0.43).
Conclusions: The association of vitamin D insufficiency with MS outcome in children with ADS appears to relate, in part, to skin pigmentation. Further work is required to delineate the complex interplay between dietary vitamin D ingestion, sun exposure and pigmentation of sun-exposed skin, seasonal vitamin D concentrations, and genetic influences of vitamin D pathways with MS risk.
