Sombekke Madeleine H, Lukas Carsten, Crusius J Bart A, Tejedor Diego, Killestein Joep, Arteta David, Martínez Antonio, Uitdehaag Bernard M J, Knol Dirk L, Peña A Salvador, Geurts Jeroen J G, De Jager Philip L, Barkhof Frederik, Vrenken Hugo, Polman Chris H
Department of Neurology, VU University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Arch Neurol. 2009 Dec;66(12):1531-6. doi: 10.1001/archneurol.2009.278.
Multiple sclerosis (MS) is a heterogeneous neurologic disease with extensive variation with respect to the most affected central nervous system region (brain vs spinal cord).
To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined.
Candidate gene study.
Academic research.
Patients were selected for the availability of DNA material, clinical variables, and brain and spinal cord magnetic resonance images (evaluating T2-weighted lesion load in the brain and the number of spinal cord lesions).
For genotyping, we used a DNA chip containing a set of genes mentioned in previous publications noting their relation to different phenotypes of MS. We assessed the association between brain and spinal cord abnormalities and the genotypes of the patients.
One hundred fifty patients were included in the analysis. Five single-nucleotide polymorphisms within the major histocompatibility complex region were associated with the number of focal abnormalities in the spinal cord. The most significant was rs3135388 (surrogate marker for the HLA-DRB11501 allele). Carriers of HLA-DRB11501 had a median of 4 spinal cord lesions compared with 2 lesions for noncarriers (P < .001). No significant association was noted between the single-nucleotide polymorphisms and T2-weighted lesion load in the brain.
Carriership of HLA-DRB11501 (via rs3135388) was associated with the extent of focal abnormalities in the spinal cord. Spinal cord lesions might be an explanation for increased MS disease severity in patients carrying HLA-DRB11501.
多发性硬化症（MS）是一种异质性神经疾病，在最易受影响的中枢神经系统区域（脑与脊髓）方面存在广泛差异。
检验病变部位（脑与脊髓）的这种差异可能（部分）由基因决定这一假设。
候选基因研究。
学术研究机构。
入选患者需具备DNA材料、临床变量以及脑和脊髓磁共振图像（评估脑内T2加权病变负荷和脊髓病变数量）。
基因分型时，我们使用了一种DNA芯片，其中包含先前出版物中提到的一组基因，并注明了它们与MS不同表型的关系。我们评估了脑和脊髓异常与患者基因型之间的关联。
150名患者纳入分析。主要组织相容性复合体区域内的5个单核苷酸多态性与脊髓局灶性异常数量相关。最显著的是rs3135388（HLA - DRB11501等位基因的替代标记）。HLA - DRB11501携带者脊髓病变中位数为4个，而非携带者为2个（P <.001）。未发现单核苷酸多态性与脑内T2加权病变负荷之间存在显著关联。
HLA - DRB11501（通过rs3135388）携带者与脊髓局灶性异常程度相关。脊髓病变可能是携带HLA - DRB11501的患者MS疾病严重程度增加的一个解释。
