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Genetic and Environmental Risk Factors in Beryllium Sensitization and Chronic Beryllium Disease* FREE TO VIEW

Lisa Maier, MD, MSPH, FCCP; John Martyny, PhD; Margaret Mroz, MSPH; Diedre McGrath, MD; Penny Lympany, PhD; Roland duBois, MD; Lenning Zhang, MS; James Murphy, PhD; Lee S. Newman, MD, MA, FCCP
Author and Funding Information

*From the National Jewish Medical and Research Center (Drs. Maier, Newman, Martyny, and Murphy; Ms. Mroz, and Ms. Zhang), Denver, CO; and National Heart and Lung Institute (Drs. Lympany, McGrath, and duBois), London, England, UK.

Correspondence to: Lisa A. Maier, MD, MSPH, FCCP, Division of Environmental and Occupational Health Sciences, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206



Chest. 2002;121(3_suppl):81S. doi:10.1378/chest.121.3_suppl.81S
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Exposure to beryllium in the workplace can result in beryllium sensitization (BeS) and chronic beryllium disease (CBD). Previous studies indicate that the presence of a glutamic acid at residue 69 in the human leukocyte antigen (HLA)-DPB1 gene (Glu69) is associated with CBD, while markers of BeS are unknown to date. Other risk factors for disease and sensitization include work as a machinist, which produces respirable particulate. To our knowledge, no study has evaluated genetic and exposure factors in combination in predicting BeS and CBD. The purpose of this study was to test the hypothesis that HLA-DPB Glu69 in concert with beryllium exposure leads to BeS as well as CBD. A nested case-control study was conducted using case patients with BeS (n = 4) and CBD (n = 7), and control subjects exposed to beryllium without evidence of BeS or CBD (n = 115), from a machining facility. Total beryllium exposure and exposure to particles < 6 μm and < 1 μm in diameter were measured. Genomic DNA was extracted from peripheral blood, and HLA-DPB1 genotyping was determined by polymerase chain reaction sequence-specific primers. A higher phenotypic frequency of the DPB1 Glu69 gene was found in case patients with BeS (4 of 4 patients) and CBD (5 of 7 patients) with 82% of case patients combined, compared to 38% of the control subjects (44 of 115 control subjects, p = 0.008). Nine of 11 case patients (82%) worked as machinists compared with 71 of 115 control subjects (63%). Using logistic regression modeling, Glu69 positivity was the only variable that contributed statistically significantly to BeS/CBD (p = 0.01; odds ratio [OR], 7.8; 95% confidence interval [CI], 1.6 to 38.5). However, work as a machinist (p = 0.17; OR, 3.17; 95% CI, 0.6 to 16.5) and lifetime-weighted average exposure to beryllium < 1 μm in diameter (p = 0.12; OR could not be estimated) along with smoking status (p = 0.22; OR, 0.4; 95% CI, 0.1 to 1.7) contributed to the model, confirming a role for exposure in BeS/CBD. Of note, because of our small sample size, our exposure variables only had 4 to 28% power to predict BeS/CBD in this study. We conclude that DPB1 Glu69 is a marker of BeS and not specific for CBD. Although not statistically significant, our data suggest that exposure variables, including working as a machinist and exposure to particles < 1 μm in size, are important in conferring susceptibility to BeS and CBD. A larger study will be needed to better delineate the contribution of exposure and its interaction with genetic susceptibility factors in BeS and CBD.

Abbreviations: BeS = beryllium sensitization; CBD = chronic beryllium disease; CI = confidence interval; HLA = human leukocyte antigen; OR = odds ratio


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