title: Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers.
abstract: BACKGROUND
  Beryllium sensitization (BeS) and chronic beryllium disease (CBD) are determined by at least one genetic factor, a glutamic acid at position 69 (E69) of the HLA-DPB1 gene, and by exposure to beryllium. The relationship between exposure and the E69 genotype has not been well characterized.
  
  
  OBJECTIVE
  The study goal was to define the relationship between beryllium exposure and E69 for CBD and BeS.
  
  
  METHODS
  Workers (n = 386) from a U.S. nuclear weapons facility were enrolled into a case-control study (70 BeS, 61 CBD, and 255 control subjects). HLA-DPB1 genotypes were determined by sequence-specific primer-polymerase chain reaction. Beryllium exposures were reconstructed on the basis of worker interviews and historical exposure measurements.
  
  
  RESULTS
  Any E69 carriage increased odds for CBD (odds ratio [OR], 7.61; 95% confidence interval [CI], 3.66-15.84) and each unit increase in lifetime weighted average exposure increased the odds for CBD (OR, 2.27; 95% CI, 1.26-4.09). Compared with E69-negative genotypes, a single E69-positive *02 allele increased the odds for BeS (OR, 12.01; 95% CI, 4.28-33.71) and CBD (OR, 3.46; 95% CI, 1.42-8.43). A single non-*02 E69 allele further increased the odds for BeS (OR, 29.54; 95% CI, 10.33-84.53) and CBD (OR, 11.97; 95% CI, 5.12-28.00) and two E69 allele copies conferred the highest odds for BeS (OR, 55.68; 95% CI, 14.80-209.40) and CBD (OR, 22.54; 95% CI, 7.00-72.62).
  
  
  CONCLUSIONS
  E69 and beryllium exposure both contribute to the odds of CBD. The increased odds for CBD and BeS due to E69 appear to be differentially distributed by genotype, with non-*02 E69 carriers and E69 homozygotes at higher odds than those with *02 genotypes.
authors.affiliation: National Jewish Health, Denver, CO 80206, USA. vandykem@NJHealth.org
authors.forename: Mike V
authors.initials: MV
authors.lastname: Van Dyke
authors.forename: John W
authors.initials: JW
authors.lastname: Martyny
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Mroz
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Silveira
authors.forename: Matt
authors.initials: M
authors.lastname: Strand
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001607:Berylliosis / Q000235:genetics*; D001608:Beryllium / Q000633:toxicity*; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D054043:Nuclear Weapons; D016273:Occupational Exposure; D016017:Odds Ratio; D016133:Polymerase Chain Reaction
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D001608:Beryllium