title: Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition.
abstract: BACKGROUND
  HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort.
  
  
  METHODS
  We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients.
  
  
  RESULTS
  Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy.
  
  
  CONCLUSIONS
  This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.
authors.affiliation: Department of Neurology, The Royal Melbourne Hospital, Melbourne, Australia. Anneke.vanderwalt@mh.org.au
authors.forename: Anneke
authors.initials: A
authors.lastname: Van der Walt
authors.forename: J
authors.initials: J
authors.lastname: Stankovich
authors.forename: M
authors.initials: M
authors.lastname: Bahlo
authors.forename: B V
authors.initials: BV
authors.lastname: Taylor
authors.forename: I A F
authors.initials: IA
authors.lastname: Van der Mei
authors.forename: S J
authors.initials: SJ
authors.lastname: Foote
authors.forename: J P
authors.initials: JP
authors.lastname: Rubio
authors.forename: T J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: H
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D017668:Age of Onset; D001284:Atrophy; D001315:Australia; D001921:Brain / Q000473:pathology*; D003071:Cognition; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D009483:Neuropsychological Tests; D010641:Phenotype; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen