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Exposure assessment
Original research
HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease
  1. James Crooks1,
  2. Margaret M Mroz2,
  3. Michael VanDyke3,
  4. Alison McGrath4,
  5. Christine Schuler5,
  6. Erin C McCanlies6,
  7. M Abbas Virji5,
  8. Kenneth D Rosenman7,
  9. Milton Rossman8,
  10. Carol Rice9,
  11. Dimitri Monos10,
  12. Tasha E Fingerlin11,
  13. Lisa A Maier2,12
  1. 1Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA
  2. 2Department of Medicine, National Jewish Health, Denver, Colorado, USA
  3. 3Department of Environmental & Occupational Health, Colorado School of Public Health, Aurora, Colorado, USA
  4. 4Environmental Health and Safety, University of Colorado, Denver, Colorado, USA
  5. 5DRDS/Field Studies Branch, U.S. National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA
  6. 6HELD, Health Effects Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA
  7. 7Department of Medicine, Michigan State University, East Lansing, Michigan, USA
  8. 8Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  9. 9Department of Environmental & Public Health Sciences, University of Cincinnati, Cincinnati, Ohio, USA
  10. 10Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  11. 11Center for Genes, Environment & Health, National Jewish Health, Denver, Colorado, USA
  12. 12Department of Medicine, University of Colorado, Denver, Colorado, USA
  1. Correspondence to Dr Lisa A Maier, Department of Medicine, National Jewish Health, Denver, Colorado, USA; maierl{at}njhealth.org

Abstract

Objectives Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case–control study assessed the contribution of genetics and exposure in the development of BeS and CBD.

Methods Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers’ job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity.

Results Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS.

Conclusions Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.

  • occupational health
  • metals
  • genetic predisposition to disease
  • lung diseases
  • interstitial

Data availability statement

No data are available.

https://doi.org/10.1136/oemed-2021-107736

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    Data availability statement

    No data are available.

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    Footnotes

    • JC and MMM are joint first authors.

    • Contributors JC and MMM analysed the data and wrote the manuscript. LAM and TEF conceived the idea for the study, provided DNA samples, patient information and oversaw the conduct of the study. LAM, CS, ECM, KDR and MR provided DNA samples, patient information, exposure data and critically contributed to the interpretation of results. MVD, AM, MAV, CR provided industrial hygiene data, exposure estimates and analysed the exposure data. DM and LAM provided genotyping and interpretation. All authors contributed to the interpretation of the results, revisions of the manuscript and approved the final version for submission.

    • Funding NIH Grants: P01 ES11810-06A1 and UL1 TR000154 from NIH/NCATS.

    • Disclaimer The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the National Institute for Occupational Safety and Health, Centres for Disease Control and Prevention.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.