title: Chronic cerebrospinal vascular insufficiency is not associated with HLA DRB1*1501 status in multiple sclerosis patients.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Neurology, State University of New York, Buffalo, New York, United States of America.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
authors.forename: Miriam
authors.initials: M
authors.lastname: Tamaño-Blanco
authors.forename: Karen
authors.initials: K
authors.lastname: Marr
authors.forename: Darlene
authors.initials: D
authors.lastname: Badgett
authors.forename: Ellen
authors.initials: E
authors.lastname: Carl
authors.forename: Makki
authors.initials: M
authors.lastname: Elfadil
authors.forename: Cheryl
authors.initials: C
authors.lastname: Kennedy
authors.forename: Ralph H B
authors.initials: RH
authors.lastname: Benedict
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology; D018615:Ultrasonography, Doppler, Color; D014689:Venous Insufficiency / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen