Rosche Berit, Cepok Sabine, Stei Susanne, Vogel Friederike, Grummel Verena, Hoffmann Steve, Kroner Antje, Mäurer Mathias, Rieckmann Peter, Sommer Norbert, Hemmer Bernhard
Clinical Neuroimmunology Group, Department of Neurology, Philipps-University, Marburg, Germany; Department of Neurology, Heinrich-Heine-University, Duesseldorf, Germany.
J Neuroimmunol. 2004 Nov;156(1-2):171-7. doi: 10.1016/j.jneuroim.2004.07.001.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). Although the cause of MS is still uncertain, it is well accepted that both genetic and environmental factors are important for the development of disease. In this study, we focused on the Polio Virus Receptor (PVR) and Herpesvirus entry mediator B (HVEB) receptor genes, which are located on chromosome 19q13, a region previously linked to MS. Both receptors are expressed in the brain and immune system and play an important role for inter-cellular adhesion and entry of neurotropic viruses to the brain. We identified four new polymorphisms in the PVR gene, which were located in the promoter region and three different exons. All exonic polymorphisms altered the amino acid sequence of the receptor. No new polymorphisms were found in the HVEB gene, but we confirmed a previously identified intronic polymorphism. We analyzed the frequency of the polymorphisms by RFLP analysis in sporadic MS patients, MS families, and healthy controls and determined the surface expression of HVEB and PVR on peripheral blood monocytes. We did not find differences in the frequency of the polymorphisms or surface expression between MS patients and controls. Overall, our findings do not support a role of HVEB and PVR genes in the development of MS.
多发性硬化症(MS)是一种中枢神经系统(CNS)的慢性炎症性脱髓鞘疾病。尽管MS的病因仍不明确,但人们普遍认为遗传和环境因素对该疾病的发展都很重要。在本研究中,我们聚焦于脊髓灰质炎病毒受体(PVR)和疱疹病毒进入介质B(HVEB)受体基因,它们位于19号染色体q13区域,该区域先前与MS相关。这两种受体均在大脑和免疫系统中表达,并且在细胞间黏附以及嗜神经病毒进入大脑过程中发挥重要作用。我们在PVR基因中鉴定出四个新的多态性位点,它们位于启动子区域和三个不同的外显子中。所有外显子多态性均改变了受体的氨基酸序列。在HVEB基因中未发现新的多态性位点,但我们证实了一个先前已鉴定出的内含子多态性。我们通过RFLP分析在散发性MS患者、MS家系和健康对照中分析了多态性的频率,并测定了外周血单核细胞上HVEB和PVR的表面表达。我们未发现MS患者与对照在多态性频率或表面表达上存在差异。总体而言,我们的研究结果不支持HVEB和PVR基因在MS发病过程中起作用。