School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
PLoS One. 2021 Dec 2;16(12):e0261097. doi: 10.1371/journal.pone.0261097. eCollection 2021.
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.
维生素 D 状态不佳（25-羟维生素 D，25(OH)D）是多发性硬化症（MS）发病的一个复现风险因素，多种维生素 D 相关的单核苷酸多态性（SNP）与 MS 发病风险升高相关。然而，关于维生素 D 补充对 MS 患者的获益的研究结果并不一致。在此，我们探索维生素 D 相关 SNP 与 MS 风险等位基因是否会影响维生素 D 补充的血清学反应。
SOLARIUM 研究的 34 名参与者同意进行基因分型，其中 26 名参与者有维生素 D 数据。SOLARIUM 研究将复发性缓解型 MS 患者随机分为安慰剂组或 14000IU 维生素 D3 组，治疗 48 周。参与者被分为 4 个 SNP 的风险等位基因“携带者”或“非携带者”：两个与维生素 D 结合蛋白（DBP）相关，与较低的 25(OH)D 水平相关（rs4588 和 rs7041），两个与维生素 D 代谢酶 CYP27B1 和 CYP24A1 相关，与 MS 发病风险升高相关（rs12368653；rs2248359，分别）。在基线和 48 周时测定 25(OH)D 水平。
DBP 相关 SNP 在基线时 25(OH)D 状态无差异，但 rs7041 风险等位基因携带者与非携带者相比，补充 48 周后 25(OH)D 水平更低（中位数 224.2 与 332.0nmol/L，p=0.013）。CYP 相关 SNP 基线时无差异，但 rs12368653 风险等位基因携带者与非携带者相比，补充 48 周后 25(OH)D 水平更高（中位数 304.1 与 152.0nmol/L，p=0.014）。
维生素 D 相关 SNP 影响大剂量维生素 D 补充的血清学反应。需要进一步研究这种改变的反应对更常见剂量的维生素 D 的影响以及其临床后果。
