The association between HLA-DPB1Glu69 and chronic beryllium disease and beryllium sensitization

Am J Ind Med. 2004 Aug;46(2):95-103. doi: 10.1002/ajim.20045.


Background: Several case-control studies have found an association between chronic beryllium disease (CBD) and HLA-DPB1 gene variants. However, the relationship between HLA-DPB1 and beryllium sensitization, and whether the presence of one or two HLA-DPB1(Glu69) alleles is differentially associated with CBD and beryllium sensitization have not been completely resolved.

Methods: Restriction fragment length polymorphism (RFLP) analysis was used to address these questions in a large population-based cohort consisting of 884 beryllium workers (90 with CBD, 64 beryllium sensitized).

Results: HLA-DPB1(Glu69) was associated with both CBD (OR = 9.4; 95% CI = 5.4, 16.6) and sensitization (OR = 3.3, 95% CI = 1.9, 5.9). Further, workers with CBD and sensitization were more likely to be homozygous HLA-DPB1(Glu69) compared to workers without disease or sensitization (P < 0.001).

Conclusions: Follow-up of this cohort, scrutiny of HLA-DPB1 haplotypes, and evaluation of gene-environment and gene-gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease.

Publication types

  • Multicenter Study

MeSH terms

  • Alleles
  • Berylliosis / genetics*
  • Berylliosis / immunology
  • Chronic Disease
  • Genotype
  • Glutamic Acid / genetics
  • HLA-DP Antigens / genetics*
  • HLA-DP beta-Chains
  • Humans
  • Polymorphism, Restriction Fragment Length
  • Seroepidemiologic Studies


  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Glutamic Acid