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 ¼ 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk (P ¼ 7 Â 10 245 ), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 (P ¼ 5 Â 10 27 ). 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.

Analysis of HLA-DRB1*1501 in Multiple Sclerosis Patients in Khuzestan Province, Iran

“…In the Australian study association of HLA-DRB1*1501 with clinical course of multiple sclerosis patients was proved [28]. Even though in this present study no statistically significant dif-…”

Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort

“…Previous studies of Australian MS patients have shown that the HLA-DRB1*1501 allele is the major risk-associated allele as in other Caucasian populations and that the DRB1*0301 allele also increases risk in non-DRB1*1501 carriers [20,21]. However, this is the first study in which the influence of HLA-DRB1 alleles and allele interactions on the frequency of OCB has been investigated.…”

Genetics of primary progressive multiple sclerosis

“…The direction of the trend was not provided. An Australian case-control study of 984 RRMS, 246 PPMS, and 1210 healthy controls investigated the associations between HLA-DRB1*01, *03, *04, *07, *11, *13, and *15 alleles and MS susceptibility and disease course (Stankovich et al, 2009). Gene dose-dependent effects of HLA-DRB1*15 and HLA-DRB1*03 alleles on MS susceptibility were identified.…”