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Patients with multiple sclerosis carry DQB1 genes which encode shared polymorphic amino acid sequences.

F Vartdal1, L M Sollid, B Vandvik

  • 1Institute of Transplantation Immunology, National Hospital, Oslo, Norway.

Human Immunology
|June 1, 1989
PubMed
Summary

Nearly all Norwegian multiple sclerosis (MS) patients studied had specific HLA types. These patients also shared amino acid sequences in their HLA-DQ beta chains, suggesting this may be the primary genetic link to MS.

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Sex and age at diagnosis are correlated with the HLA-DR2, DQ6 haplotype in multiple sclerosis.

Journal of the neurological sciences·2000

Area of Science:

  • Immunogenetics
  • Neurology

Background:

  • Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
  • Previous studies have identified associations between specific Human Leukocyte Antigen (HLA) types, particularly HLA-DR alleles, and MS susceptibility.

Purpose of the Study:

  • To investigate the association of HLA-DR2, HLA-DR4, and HLA-DRw6 with multiple sclerosis in a Norwegian cohort.
  • To explore the role of HLA-DQB1 genes and their encoded amino acid sequences in the observed HLA-DR associations with MS.

Main Methods:

  • Genotyping of 61 Norwegian multiple sclerosis patients for HLA-DR specificities DR2, DR4, and DRw6.
  • Sequence-specific oligonucleotide probe typing to identify HLA-DQB1 genes.
  • Analysis of shared polymorphic amino acid sequences in the HLA-DQ beta chains.

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Main Results:

  • 97% (59 out of 61) of the patients were positive for at least one of the studied HLA-DR specificities.
  • The same 59 patients carried HLA-DQB1 genes associated with DR2, DR4, or DRw6.
  • These associated HLA-DQB1 genes encoded shared polymorphic amino acid sequences in the membrane-distal region of the HLA-DQ beta chains.

Conclusions:

  • The findings suggest that a shared polymorphism in the HLA-DQ beta chain may be the primary genetic factor associated with multiple sclerosis.
  • This shared DQ beta polymorphism could potentially explain the previously observed associations with specific HLA-DR types in MS.