HLA-DRB1*1501 and spinal cord magnetic resonance imaging lesions in multiple sclerosis

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 DNAmaterial, 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.Weassessed 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