HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients

The MHC region has been shown to contain a susceptibility locus for multipl e sclerosis (MS). While the strongest association to date has been between HLA-DRB1*1501 and MS, the exact nature of the MHC association in MS remains unclear. Two candidate polymorphic loci within the MHC class II region, th e HLA-DMB gene and the HLA-DRA promoter, which lie close to HLA-DRB1, were therefore examined in an Australian MS population. The HLA-DMB*0103 phenoty pe was increased in the MS patients (46% vs. 30%) and the frequency of the HLA-DRA promoter A allele was also increased (81% vs. 68%). When the subjec ts were stratified into HLA-DRB1*1501 positive and negative individuals the se associations were not significantly different. This is a result of the s trong linkage disequilibrium between HLA-DRB1*1501 and both HLA-DMB*0103 an d the HLA-DRA promoter A allele. The complete linkage between DRB1*1501 and the HLA-DRA promoter A allele indicates that the MS susceptibility haploty pe (DRB1*1501-HLA-DQB1*0602-HLA-DQA1*0102) can be extended out to promoter of the HLA-DRA locus. Interactions between both HLA-DMB and the HLA-DRA pro moter and other reported MS susceptibility loci were examined (TCRBV polymo rphisms, HLA-DQA1 and HLA-DQB1). Some interactions between specific TCRBV p olymorphisms and the HLA-DRA promoter were observed, which is consistent wi th other published reports suggesting an epistatic interaction between TCRB V and HLA-DRB1. (C) American Society for Histocompatibility and Immunogenet ics, 1999. Published by Elsevier Science Inc.