HLA-DPB1 E69 Genotype and Exposure in Beryllium Sensitisation and Disease

Details

• Personal Author:
  Crooks J ; Fingerlin TE ; Maier LA ; McCanlies EC ; McGrath A ; Monos D ; Mroz MM ; Rice C ; Rosenman, Kenneth D. ; Rossman M ; Schuler C ; VanDyke M ; Virji, M. Abbas
• Description:
  Objectives: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the beta 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. [Description provided by NIOSH]
• Subjects:
  Antigens Genetics Hypersensitivity Occupational Health Safety
• Keywords:
  Beryllium Disease Gene Mutation Genes Genotype Leukocytes Nested Case Control Studies Sensitization
• ISSN:
  1351-0711
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; Michigan ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 8 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  RHD - Respiratory Health Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  120-126
• Volume:
  79
• Issue:
  2
• NIOSHTIC Number:
  nn:20063541
• Citation:
  Occup Environ Med 2022 Feb; 79(2):120-126
• Contact Point Address:
  Dr Lisa A Maier, Department of Medicine, National Jewish Health, Denver, Colorado, USA
• Email:
  maierl@njhealth.org
• CAS Registry Number:
  L-Glutamic acid (CAS RN 56-86-0)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Public Safety
• Peer Reviewed:
  True
• Source Full Name:
  Occupational and Environmental Medicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:05ef6f06a52c09a00ecad57fce920e70e24c876d81fb4d59313629bb984d256baab69cd4a2aedbefd6bfaba796ef1bfcfb682e62664147284220399d8928f350
• Download URL:
  https://stacks.cdc.gov/view/cdc/222130/cdc_222130_DS1.pdf
• File Type:
  [PDF - 805.93 KB ]