HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis.

Human leucocyte antigen (HLA)-DRB11501 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 DRB11501 was strongly associated with risk (P = 7 x 10(-45)), as expected, and after adjusting for DRB11501, a predisposing effect was also observed for DRB103 (P = 5 x 10(-7)). Individuals homozygous for either DRB115 or DRB103 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB104 and the DRB101/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.