HLA-DQ POLYMORPHISMS DO NOT EXPLAIN HLA CLASS-II ASSOCIATIONS WITH MULTIPLE-SCLEROSIS IN 2 CANADIAN PATIENT GROUPS

Patient sharing of HLA-DQ allelic polymorphisms is a possible explanation for the association of multiple sclerosis (MS) with different HLA class II haplotypes in different populations. We used two-locus linkage analysis to investigate the relevance of three different polymorphisms to MS susceptibility in 79 French Canadian patients and 62 mixed ethnic white patients. In French Canadians, we found that an MS association with shared DQB1 sequences and a DQA1 codon for glutamine at residue 34 is secondary to an MS association with the common DR2 haplotype, DRB1*1501-DQA1*0102-DQB1*0602. In contrast, we found that an MS association in French Canadians with a DQB1 codon for leucine at residue 26 (DQbetaLeu26) is not secondary to an MS association with the DR2-bearing haplotype. Mixed ethnic whites showed a positive MS association with the DR2 haplotype but no MS association with any of these polymorphisms. We conclude that (1) the DR2 haplotype is predispositional for MS in both populations, (2) DQbetaLeu26 is an additional predispositional factor in French Canadians, and (3) none of the DQ polymorphisms fully explains the association of MS with HLA alleles in both patient groups.