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1.  Risk of Chronic Beryllium Disease by HLA-DPB1 E69 Genotype and Beryllium Exposure in Nuclear Workers 
Rationale: 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.
Objectives: 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.
Measurements and Main 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.
doi:10.1164/rccm.201002-0254OC
PMCID: PMC3136994  PMID: 21471109
berylliosis; genetics; case–control studies; occupational exposure; HLA-DP antigens

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