HLA-DR, HLA-DQA1 AND HLA-DQB1 ASSOCIATIONS IN AUSTRALIAN MULTIPLE-SCLEROSIS PATIENTS

Molecular genotyping for the major histocompatibility complex (MHC) cl ass II loci, HLA-DRB1, -DQB1 and -DQA1, in 100 patients with relapsing /remitting multiple scerlosis (MS) demonstrated an association with th e HLA-DR2, DQw6-associated alleles DRB11501, DQB1*0602 and DQA1*0102, thereby extending this finding among MS patients in several countries to an Australian population. Analysis by the relative predispositiona l effect (RPE) method provided no evidence for a second susceptibility allele at either DQA1 or DQB1. However, our data and that of others s uggest a negative association with DQA10101. Associations were found with DQB1 alleles sharing sequence homology with DQB10602, with DQB1 alleles encoding leucine at residue 26 (Leu 26), with DQA1 alleles enc oding glutamine at residue 34 (Gln 34) and with Leu 26 plus Gln 34 all eles, but each was shown by two-loci linkage analysis to be secondary to the DRB11501, DQB1*0602, DQA1*0102 association. The recently repor ted negative association with DQA1 alleles encoding phenylalanine at a mino acid 25, leucine at amino acid 69 and arginine at amino acid 52 w as not found in this study, although there was a trend towards reduced phenylalanine at amino acid 25. The determination at a molecular leve l of an explanation for the world-wide association with these alleles remains elusive despite major advances in MHC typing.