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HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis
journal contribution
posted on 2023-05-17, 01:14 authored by Jim Stankovich, Butzkueven, H, Marriott, M, Chapman, C, Tubridy, N, Tait, BD, Varney, MD, Bruce TaylorBruce Taylor, Simon James FooteSimon James Foote, Booth, DR, Broadley, S, Greer, JM, Griffiths, LR, Heard, RN, Lechner-Scott, J, Pender, MJ, Scott, RJ, Stewart, GJ, Kilpatrick, TJ, Rubio, JPHuman 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 largesample 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.
History
Publication title
Tissue AntigensVolume
74Pagination
17-21ISSN
0001-2815Department/School
Menzies Institute for Medical ResearchPublisher
Blackwell MunksgaardPlace of publication
35 Norre Sogade, Po Box 2148, Copenhagen, Denmark, Dk-1016Repository Status
- Restricted