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Article Abstract
Background: 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).
Objective: To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined.
Design: Candidate gene study.
Setting: Academic research.
Patients: 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).
Main Outcome Measures: 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.
Results: 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-DRB1*1501 allele). Carriers of HLA-DRB1*1501 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.
Conclusions: Carriership of HLA-DRB1*1501 (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-DRB1*1501.
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| http://dx.doi.org/10.1001/archneurol.2009.278 | DOI Listing |
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