Department of Clinical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava and University Hospital Martin, Martin, Slovak Republic.
Clinic of Neurology, Jessenius Faculty of Medicine, Comenius University in Bratislava and University Hospital Martin, Martin, Slovak Republic.
Neurol Res. 2023 Oct;45(10):912-918. doi: 10.1080/01616412.2023.2247195. Epub 2023 Aug 15.
Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB115. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB115:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB115:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A - 0.181 in patients vs. 0.161 in controls, OR = 1.15, .95 CI = 0.90-1.47, = 0.289). The logistic regression analysis, adjusted for sex and age, showed no differences in Cdx-2 genotype counts when using an additive, dominant or recessive genetic model ( = 0.351, 0.150, 0.240 respectively). The Cdx-2 variants were also not associated with disease disability progression, evaluated using the Multiple Sclerosis Severity Score. The HLA-DRB115:01 allele was found to strongly increase the risk of MS in our study (0.300 in patients vs. 0.101 in controls, OR = 3.83, .95 CI = 2.94-4.99, = 1.016 × 10, dominant genetic model OR = 4.62, .95 CI = 3.40-6.26, = 9.1 × 10). In summary, we found the Cdx-2 as a single genetic marker not to be associated with MS development or progression in Slovaks, independently of HLA-DRB1*15:01 status.
维生素 D 缺乏症与多发性硬化症（MS）的发病机制有关，MS 是一种严重的中枢神经系统自身免疫性脱髓鞘疾病。基因多态性 Cdx-2（rs11568820，G/A）严重影响维生素 D 受体（VDR）的转录活性，VDR 与包括 HLA-DRB115 在内的靶基因的维生素 D 反应元件结合。本研究旨在分析 Cdx-2 变异与 MS 风险和残疾进展的关系，并评估 DRB115:01 等位基因是否为可能的混杂因素。本研究共纳入 493 例 MS 患者和 417 例健康对照者。采用限制性分析检测 Cdx-2 基因分型；采用高分辨率熔解分析其替代标志物 rs3135388（G/A）检测 DRB115:01 阳性。我们的结果未证明 Cdx-2 与 MS 风险（次要等位基因 A-0.181 在患者中与 0.161 在对照组中，OR=1.15，95%CI=0.90-1.47，=0.289）之间存在等位基因关联。经性别和年龄调整的 logistic 回归分析显示，采用加性、显性或隐性遗传模型时，Cdx-2 基因型计数无差异（=0.351、0.150、0.240）。Cdx-2 变异与我们使用多发性硬化严重程度评分评估的疾病残疾进展也无关。在本研究中，HLA-DRB115:01 等位基因被发现可显著增加 MS 的风险（0.300 在患者中与 0.101 在对照组中，OR=3.83，95%CI=2.94-4.99，=1.016×10，显性遗传模型 OR=4.62，95%CI=3.40-6.26，=9.1×10）。总之，我们发现 Cdx-2 作为单一遗传标记，在不考虑 HLA-DRB1*15:01 状态的情况下，与斯洛伐克人的 MS 发病或进展无关。
