Vitamin D genes influence MS relapses in children.

Vitamin D genes influence MS relapses in children.

Publication date: May 13, 2019

The aim of this study was to determine whether a vitamin D genetic risk score (vitDGRS) is associated with 25-hydroxyvitamin D (25(OH)D) level and multiple sclerosis (MS) relapses in children.

DNA samples were typed for single nucleotide polymorphisms (SNPs) from four genes previously identified to be associated with 25(OH)D levels. SNPs with strong associations with 25(OH)D after multiple comparison correction were used to create a genetic risk score (vitDGRS). Cox regression models tested associations of vitDGRS with relapse hazard.

Two independent SNPs within or near GC and NADSYN1/DHCR7 genes were strongly associated with 25(OH)D levels in the discovery cohort ( n = 182) after Bonferroni correction. The vitDGRS of these SNPs explained 4.5% of the variance of 25(OH)D level after adjustment for genetic ancestry. Having the highest versus lowest vitDGRS was associated with 11 ng/mL lower 25(OH)D level (95% confidence interval (CI) = -17.5, -4.5, p = 0.001) in the discovery cohort. Adjusting for ancestry, sex, disease-modifying therapy (DMT), and HLA-DRB1*15 carrier status, the highest versus lowest vitDGRS was associated with 2.6-fold (95% CI = 1.37, 5.03, p = 0.004) and 2.0-fold (95% CI = 0.75, 5.20, p = 0.16) higher relapse hazard in the discovery and replication cohorts, respectively.

The vitDGRS identifies children at greater risk of relapse. These findings support a causal role for vitamin D in MS course.

Graves, J.S., Barcellos, L.F., Krupp, L., Belman, A., Shao, X., Quach, H., Hart, J., Chitnis, T., Weinstock-Guttman, B., Aaen, G., Benson, L., Gorman, M., Greenberg, B., Lotze, T., Soe, M., Ness, J., Rodriguez, M., Rose, J., Schreiner, T., Tillema, J.M., Waldman, A., Casper, T.C., and Waubant, E. Vitamin D genes influence MS relapses in children. 17984. 2019 Mult Scler.

Concepts Keywords
Cohort Multiple sclerosis
Confidence Interval Polygenic score
Cox Regression Vitamin C
DMT Single-nucleotide polymorphism
DNA RTT
Genetic Vitamins
HLA Biomolecules
Multiple Comparison Mutation
Multiple Sclerosis Branches of biology
Relapse Pediatric multiple sclerosis
Single Nucleotide Polymorphisms MS
SNPs Ancestry sex disease
Variance Carrier status
Vitamin

Semantics

Type Source Name
gene UNIPROT HLA-DRB1
gene UNIPROT DMTN
gene UNIPROT DHCR7
gene UNIPROT NADSYN1
gene UNIPROT COX5A
gene UNIPROT COX8A
gene UNIPROT CPOX
disease MESH multiple
disease DOID multiple sclerosis
disease MESH multiple sclerosis
gene UNIPROT DNMT1
gene UNIPROT CD69
gene UNIPROT CD5L
disease MESH relapses
drug DRUGBANK Vitamin D

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