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- Title
Risk of chronic beryllium disease by HLA-DPB1 E69 genotype and beryllium exposure in nuclear workers.
- Authors
Van Dyke MV; Martyny JW; Mroz MM; Silveira LJ; Strand M; Fingerlin TE; Sato H; Newman LS; Maier LA; Van Dyke, Mike V; Martyny, John W; Mroz, Margaret M; Silveira, Lori J; Strand, Matt; Fingerlin, Tasha E; Sato, Hiroe; Newman, Lee S; Maier, Lisa A
- Abstract
<bold>Rationale: </bold>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.<bold>Objectives: </bold>The study goal was to define the relationship between beryllium exposure and E69 for CBD and BeS.<bold>Methods: </bold>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.<bold>Measurements and Main Results: </bold>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).<bold>Conclusions: </bold>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.
- Publication
American Journal of Respiratory & Critical Care Medicine, 2011, Vol 183, Issue 12, p1680
- ISSN
1073-449X
- Publication type
journal article
- DOI
10.1164/rccm.201002-0254OC