PT  - JOURNAL ARTICLE
AU  - James Crooks
AU  - Margaret M Mroz
AU  - Michael VanDyke
AU  - Alison McGrath
AU  - Christine Schuler
AU  - Erin C McCanlies
AU  - M Abbas Virji
AU  - Kenneth D Rosenman
AU  - Milton Rossman
AU  - Carol Rice
AU  - Dimitri Monos
AU  - Tasha E Fingerlin
AU  - Lisa A Maier
TI  - HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease
AID  - 10.1136/oemed-2021-107736
DP  - 2022 Feb 01
TA  - Occupational and Environmental Medicine
PG  - 120--126
VI  - 79
IP  - 2
4099  - http://oem.bmj.com/content/79/2/120.short
4100  - http://oem.bmj.com/content/79/2/120.full
SO  - Occup Environ Med2022 Feb 01; 79
AB  - 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.No data are available. Individual participant data is not available.