Human leukocyte antigen DR2 (HLA-DR2) is a well-established genetic risk factor for multiple sclerosis (MS). However, it is still unknown whether this factor is associated with a specific disease phenotype, and in particular, to a regional distribution of white matter (WM) lesion phenotype on magnetic resonance imaging (MRI). On a voxel-by-voxel basis, we analyzed the T1 and T2 MRI-derived lesion maps of 50 patients with MS in order to determine the possible influence of HLA-DR2 genotype on the lesional MRI pattern at early stages of the disease. HLA-DR2 was present in 15 (30%) patients of our cohort. They displayed similar WM lesion distribution as the subjects without this factor. Thus, lesion distribution in MS seems to be independent of the DR2 genotype.