Hoppenbrouwers I A, Aulchenko Y S, Ebers G C, Ramagopalan S V, Oostra B A, van Duijn C M, Hintzen R Q
Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, The Netherlands.
Genes Immun. 2008 Jun;9(4):334-7. doi: 10.1038/gene.2008.22. Epub 2008 Apr 10.
HLA-DRB1 is the major locus associated with risk for multiple sclerosis (MS). A recent genome-wide study showed three additional single-nucleotide polymorphisms (SNPs), within the IL2RA and IL7RA genes respectively, also to be associated with MS. Consistent association but lower significance was found for 13 other SNPs. In this study, we aimed to verify association of these SNPs with MS in 46 MS patients and 194 controls from a Dutch genetically isolated population. Apart from the human leukocyte antigen locus, the EVI5 gene on chromosome 1 was confirmed as a novel risk gene, with odds ratios (ORs) even higher than those from the MS Consortium (ORs 2.01 and 1.9; P=0.01). The risk effect of EVI5 was further validated for the general MS population in an independent set of 1318 MS patients from the Canadian Collaborative Project on the Genetic Susceptibility to MS. On the basis of the transmission disequilibrium testing, a weak but significant risk effect was observed (OR 1.15; P=0.03 and OR 1.15; P=0.04). This study confirms EVI5 as another risk locus for MS; however, much of the genetic basis of MS remains unidentified.
人类白细胞抗原-DRB1（HLA-DRB1）是与多发性硬化症（MS）风险相关的主要基因座。最近一项全基因组研究表明，白细胞介素2受体α链（IL2RA）基因和白细胞介素7受体α链（IL7RA）基因内分别还有另外三个单核苷酸多态性（SNP）也与MS相关。对于其他13个SNP，发现了一致的关联性，但显著性较低。在本研究中，我们旨在验证这些SNP与来自荷兰一个遗传隔离人群的46例MS患者和194例对照之间的关联性。除了人类白细胞抗原基因座外，1号染色体上的EVI5基因被确认为一个新的风险基因，其优势比（OR）甚至高于MS协会研究中的结果（OR分别为2.01和1.9；P = 0.01）。在加拿大MS遗传易感性合作项目的另一组1318例MS患者中，对EVI5基因对普通MS人群的风险效应进行了进一步验证。基于传递不平衡检验，观察到了微弱但显著的风险效应（OR为1.15；P = 0.03和OR为1.15；P = 0.04）。本研究证实EVI5是MS的另一个风险基因座；然而，MS的许多遗传基础仍未明确。
