Ďurmanová V, Shawkatová I, Javor J, Párnická Z, Čopíková-Cundráková D, Turčáni P, Lisá I, Gajdošechová B, Buc M, Bucová M
Institute of Immunology, School of Medicine, Comenius University in Bratislava, Slovakia.
1st Department of Neurology, School of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, Slovakia.
Folia Biol (Praha). 2015;61(1):8-13. doi: 10.14712/fb2015061010008.
Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in genetically sensitive individuals. As migration of immune cells into the CNS is facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene may be considered as a plausible candidate genetic risk factor for susceptibility to MS. Therefore, the objective of our study was to investigate the association between two genetic polymorphisms located in the VLA4 gene and the risk of multiple sclerosis. One hundred seventeen MS patients and 165 control subjects from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269 (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the rs3135388 polymorphism tagging the HLA-DRB115:01 allele, which is a known genetic factor associated with susceptibility to develop MS in many populations. Our findings show for the first time that the rs3135388 polymorphism is a strong risk factor for MS in the Slovak population. Investigation of the VLA4 gene polymorphisms revealed a significantly higher frequency of the 3061AG genotype in MS patients compared to the controls (P ≤ 0.05). We suggest that the 3061AG polymorphic variant is an independent genetic risk factor for MS development in our population as it was significantly associated with this disease. The association was also confirmed after applying multivariate logistic-regression analysis adjusted for gender, age and HLA-DRB115:01 positivity as possible influencing factors.
多发性硬化症（MS）是一种发生在遗传易感性个体中的炎症性自身免疫疾病。由于极晚期抗原4（VLA-4）整合素分子促进免疫细胞向中枢神经系统迁移，VLA4基因可被视为MS易感性的一个合理候选遗传风险因素。因此，我们研究的目的是调查位于VLA4基因的两个基因多态性与多发性硬化症风险之间的关联。对来自斯洛伐克的117例MS患者和165例对照受试者进行了VLA4基因SNP多态性269位（C/A）和3061位（A/G）的基因分型。同一研究队列还进行了rs3135388多态性的基因分型，该多态性标记HLA-DRB115:01等位基因，这是许多人群中与发生MS易感性相关的已知遗传因素。我们的研究结果首次表明，rs3135388多态性是斯洛伐克人群中MS的一个强风险因素。对VLA4基因多态性的研究显示，与对照组相比，MS患者中3061AG基因型的频率显著更高（P≤0.05）。我们认为3061AG多态性变体是我们人群中MS发生的一个独立遗传风险因素，因为它与这种疾病显著相关。在对性别、年龄和HLA-DRB115:01阳性作为可能影响因素进行调整的多变量逻辑回归分析后，该关联也得到了证实。
