Vitamin D genes increase MS relapses in children by 2X

Vitamin D genes influence MS relapses in children.

Mult Scler. 2019 doi: 10.1177/1352458519845842

Graves JS1, Barcellos LF2, Krupp L3, Belman A4, Shao X2, Quach H2, Hart J1, Chitnis T5, Weinstock-Guttman B6, Aaen G7, Benson L8, Gorman M8, Greenberg B9, Lotze T10, Soe M11, Ness J12, Rodriguez M13, Rose J14, Schreiner T15, Tillema JM13, Waldman A16, Casper TC17, Waubant E1.

Items in both categories MS and Genetics are listed here: {category} 1. 2 of the 6 genes which are invisible to Vitamin D blood tests MS and Vitamin D Receptor: {category} MS and Vitamin D Binding Protein: {category} * Vitamin D Binding Protein masks how much Vitamin D gets to tissues – May 2019

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OBJECTIVE: 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.

METHODS: 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.

RESULTS:

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.

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