Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford, Oxford, UK.
J Neurol Sci. 2011 Jun 15;305(1-2):116-20. doi: 10.1016/j.jns.2011.02.032. Epub 2011 Mar 26.
Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility.
MS patients (n=1364) and their unaffected first-degree relatives (n=1661) were ascertained through the Canadian Collaborative study. Seventy-one SNPs, across four genes [vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1) enzyme, vitamin D binding protein (DBP), 24-hydroxylase (CYP24)], were genotyped and tested for association with MS susceptibility using TDT in PLINK. Secondary analyses included stratification for HLA-DRB1*15 and parent of origin transmission effects.
We found no significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03). There was no evidence for differential maternal versus paternal allele transmission.
The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage.
多发性硬化症（MS）是由基因与环境相互作用决定的，并且已经提出了维生素 D 充足的影响。先前的研究表明，血清 25-羟维生素 D（25（OH）D）水平受遗传影响。维生素 D 途径基因的多态性是与 MS 易感性相关的候选基因。
通过加拿大合作研究确定了 MS 患者（n=1364）及其未受影响的一级亲属（n=1661）。对四个基因（维生素 D 受体（VDR）、1-α-羟化酶（CYP27B1）酶、维生素 D 结合蛋白（DBP）、24-羟化酶（CYP24））中的 71 个 SNP 进行基因分型，并使用 PLINK 中的 TDT 检测其与 MS 易感性的关联。次要分析包括 HLA-DRB1*15 分层和亲本来源传递效应。
在进行多次比较校正后，我们没有发现维生素 D 途径基因与 MS 易感性之间存在显著关联。然而，VDR Fok1 变体（rs2228570）先前与 MS 易感性和 MS 患者的 25（OH）D 水平呈正相关，在 DRB15 阴性患者中显示出边缘扭曲的传递（p=0.03）。没有证据表明母体与父体等位基因传递的差异。
尽管样本量较大且基因覆盖全面，但这些发现未能直接将维生素 D 代谢基因与 MS 易感性联系起来。
