Polymorphism in an HLA linked proteasome gene influences phenotypic expression of disease in HLA-B27 positive individuals

J Rheumatol. 1994 Apr;21(4):665-9.


Objective: To investigate the potential influence of the HLA-linked LMP (low molecular weight polypeptide) genes on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS).

Methods: A polymorphic CfoI restriction enzyme site in the coding region of one proteasome gene was evaluated in 125 genomic DNA samples from B27 individuals with well documented AS, 55 of whom had had acute iritis, and 42 samples from normal, ethnically matched B27 blood donors where AS was excluded.

Results: Analysis of individuals with B27 AS with iritis revealed significant differences in allelic distribution of this biallelic locus compared to patients with B27 AS without iritis. Furthermore, homozygosity for the disease associated allele was significantly more prevalent in patients with AS with iritis (72.7%) than in patients without iritis (38.6%) (p(uncorrected) = 0.0003) or B27 controls (45.2%) (p(uncorrected) = 0.01).

Conclusion: Our findings support the involvement of additional HLA linked genes in the phenotypic expression of disease in B27 individuals and suggest a role for the non-B27 HLA haplotype in susceptibility to iritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Cysteine Endopeptidases / genetics*
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Female
  • Genetic Linkage
  • HLA-B27 Antigen / genetics*
  • Homozygote
  • Humans
  • Iritis / enzymology
  • Iritis / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multienzyme Complexes / genetics*
  • Phenotype
  • Polymorphism, Genetic*
  • Proteasome Endopeptidase Complex
  • Proteins / genetics
  • Spondylitis, Ankylosing / enzymology*
  • Spondylitis, Ankylosing / genetics*


  • DNA Primers
  • DNA, Complementary
  • HLA-B27 Antigen
  • Multienzyme Complexes
  • Proteins
  • LMP-2 protein
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex