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 explanat ion for the association of multiple sclerosis (MS) with different HLA class II haplotypes in different populations. We used two-locus linkag e analysis to investigate the relevance of three different polymorphis ms to MS susceptibility in 79 French Canadian patients and 62 mixed et hnic white patients. In French Canadians, we found that an MS associat ion with shared DQB1 sequences and a DQA1 codon for glutamine at resid ue 34 is secondary to an MS association with the common DR2 haplotype, DRB11501-DQA1*0102-DQB1*0602. In contrast, we found that an MS assoc iation in French Canadians with a DQB1 codon for leucine at residue 26 (DQbetaLeu26) is not secondary to an MS association with the DR2-bear ing haplotype. Mixed ethnic whites showed a positive MS association wi th the DR2 haplotype but no MS association with any of these polymorph isms. We conclude that (1) the DR2 haplotype is predispositional for M S in both populations, (2) DQbetaLeu26 is an additional predisposition al factor in French Canadians, and (3) none of the DQ polymorphisms fu lly explains the association of MS with HLA alleles in both patient gr oups.