Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis

• Published in: PloS one Vol. 16; no. 12; p. e0261097
• Main Authors: Mimpen, Max, Rolf, Linda, Poelmans, Geert, van den Ouweland, Jody, Hupperts, Raymond, Damoiseaux, Jan, Smolders, Joost
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.12.2021; Public Library of Science (PLoS)
• Subjects: 25-Hydroxyvitamin D; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; Adult; Alfacalcidol; Alleles; Analysis; Biology and Life Sciences; Calcifediol; Calciferol; Chromatography; Consent; Dietary Supplements; DNA-Binding Proteins - genetics; Enzymes; Female; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Genotype; Genotyping; Health aspects; Health risks; Humans; Immunoassay; Male; Mass spectrometry; Medicine and Health Sciences; Mental health; Metabolism; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; Neurosciences; Nucleotides; Physical sciences; Polymorphism, Single Nucleotide; Prognosis; Research and Analysis Methods; Risk analysis; Risk factors; Scientific imaging; Serology; Single-nucleotide polymorphism; Supplements; Transcription Factors - genetics; Vitamin D; Vitamin D - administration & dosage; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D3; Vitamin D3 24-Hydroxylase - genetics; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0261097

A poor 25-hydroxyvitamin D (25(OH)D) status is a much replicated risk factor for developing multiple sclerosis (MS), and several vitamin D-associated single nucleotide polymorphisms (SNPs) have been associated with a higher risk of MS. However, studies on the benefit of vitamin D supplementation in MS show inconclusive results. Here, we explore whether vitamin D-associated SNPs and MS risk alleles confound serological response to vitamin D supplementation. 34 participants from the SOLARIUM study consented to genotyping, of which 26 had vitamin D data available. The SOLARIUM study randomised relapsing-remitting MS patients to placebo or 14,000 IU vitamin D3 for 48 weeks. Participants were categorised as either 'carriers' or 'non-carriers' of the risk allele for 4 SNPs: two related to D binding protein (DBP) and associated with lower 25(OH)D levels (rs4588 and rs7041), and two related to vitamin D metabolism enzymes CYP27B1 and CYP24A1 and associated with a higher risk of MS (rs12368653; rs2248359, respectively). 25(OH)D levels were determined at baseline and after 48 weeks. The DBP-related SNPs showed no difference in 25(OH)D status at baseline, but carriers of the rs7041 risk allele showed lower 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 224.2 vs. 332.0 nmol/L, p = 0.013). For CYP related SNPs, neither showed a difference at baseline, but carriers of the rs12368653 risk allele showed higher 25(OH)D-levels compared to non-carriers after 48 weeks of supplementation (median 304.1 vs. 152.0 nmol/L, p = 0.014). Vitamin D-related SNPs affect the serological response to high-dose vitamin D supplementation. The effects on more common doses of vitamin D, as well as the clinical consequence of this altered response, need to be investigated further.