title: Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry.
abstract: OBJECTIVE
  Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPβ chain (DPβE69). However, the nature of the relationship between exposure and carriage of the DPβE69 genotype has not been well studied. The goal of this study was to determine the relationship between DPβE69 and exposure in BeS and CBD.
  
  
  METHODS
  Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case-control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks.
  
  
  RESULTS
  After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DPβE69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 μg/m(3). Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122).
  
  
  CONCLUSIONS
  DPβE69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DPβE69 alone appears to be similar.
authors: Hollis Laboratory, Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, Colorado 80206, USA. vandykem@njhealth.org
authors: Michael V
authors: MV
authors: Van Dyke
authors: John W
authors: JW
authors: Martyny
authors: Margaret M
authors: MM
authors: Mroz
authors: Lori J
authors: LJ
authors: Silveira
authors: Matt
authors: M
authors: Strand
authors: Donna L
authors: DL
authors: Cragle
authors: William G
authors: WG
authors: Tankersley
authors: Susan M
authors: SM
authors: Wells
authors: Lee S
authors: LS
authors: Newman
authors: Lisa A
authors: LA
authors: Maier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001607:Berylliosis / Q000235:genetics*; D001608:Beryllium / Q000633:toxicity*; D016022:Case-Control Studies; D005260:Female; D059868:HLA-DP beta-Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007221:Industry; D008297:Male; D008875:Middle Aged; D054043:Nuclear Weapons; D016273:Occupational Exposure / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D001608:Beryllium