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Background  Chronic cerebrospinal venous insufficiency (CCSVI) was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS). The objective was to assess the associations between  HLA DRB1*1501  status and the occurrence of CCSVI in MS patients.    Methodology/Principal Findings  This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study. The  HLA DRB1*1501  status was obtained in 268 MS patients and 155 controls by genotyping  rs3135005 , a SNP associated with  DRB1*1501  status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52,  p <0.001) in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of  HLA DRB1*1501  positivity (HLA + ) in MS was higher compared (OR = 2.33,  p <0.001) to 31.6% to controls. The HLA +  frequency in the non-progressive (51.6%) and progressive MS groups (52.3%) was similar. The frequency of HLA +  CCSVI +  was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of  HLA DRB1*1501  status in MS patients.    Conclusions/Significance  The lack of strong associations of CCSVI with  HLA DRB1*1501  suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS.

Chronic Cerebrospinal Vascular Insufficiency Is Not Associated with HLA DRB1*1501 Status in Multiple Sclerosis Patients