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

Hum Immunol. 1999 Sep;60(9):886-93. doi: 10.1016/s0198-8859(99)00054-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia
  • Epistasis, Genetic
  • HLA-D Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • HLA-DR alpha-Chains
  • Histocompatibility Antigens Class II*
  • Humans
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*

Substances

  • H2-M antigens
  • HLA-D Antigens
  • HLA-DM antigens
  • HLA-DR Antigens
  • HLA-DR alpha-Chains
  • Histocompatibility Antigens Class II