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 multiple 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, the 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 phenotype 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 subjects were stratified into HLA-DRB*1501 positive and negative individuals these associations were not significantly different. This is a result of the strong linkage disequilibrium between HLA-DRB*1501 and both HLA-DMB*0103 and the HLA-DRA promoter A allele. The complete linkage between DRB1*1501 and the HLA-DRA promoter A allele indicates that the MS susceptibility haplotype (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 promoter and other reported MS susceptibility loci were examined (TCRBV polymorphisms, HLA-DQA1 and HLA-DQB1). Some interactions between specific TCRBV polymorphisms and the HLA-DRA promoter were observed, which is consistent with other published reports suggesting an epistatic interaction between TCRBV and HLA-DRB1.
Bennetts
B H
BH
Department of Immunology, Westmead Hospital, Australia.
Teutsch
S M
SM
Buhler
M M
MM
Heard
R N
RN
Stewart
G J
GJ
D001315:Australia; D004843:Epistasis, Genetic; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D000949:Histocompatibility Antigens Class II