title: HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis.
abstract: Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles in a large sample of 1230 Australian MS cases, with some enrichment for subjects with primary progressive (PPMS) disease (n = 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk (P = 7 x 10(-45)), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 (P = 5 x 10(-7)). Individuals homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15 genotype combination, respectively, protected against PPMS in comparison to subjects with relapsing disease. Together, these data provide further evidence of heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the phenotypic expression of MS.
authors.affiliation: The Menzies Research Institute, Hobart, Tasmania, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Stankovich
authors.forename: H
authors.initials: H
authors.lastname: Butzkueven
authors.forename: M
authors.initials: M
authors.lastname: Marriott
authors.forename: C
authors.initials: C
authors.lastname: Chapman
authors.forename: N
authors.initials: N
authors.lastname: Tubridy
authors.forename: B D
authors.initials: BD
authors.lastname: Tait
authors.forename: M D
authors.initials: MD
authors.lastname: Varney
authors.forename: B V
authors.initials: BV
authors.lastname: Taylor
authors.forename: S J
authors.initials: SJ
authors.lastname: Foote
authors.forename: T J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: J P
authors.initials: JP
authors.lastname: Rubio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001315:Australia / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains