Genetic/exposure interaction in beryllium disease.
Rosenman-KD; Hertzberg-V; Monos-D; Rice-C; Rossman-M
Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-007495, 2008 Jan; :1-36
Rationale: CBD is a hypersensitivity granulomatous disease affecting the lungs of people exposed to the metal Beryllium (Be2+). Objective: To study the polymorphisms of the HLA class II molecules that influence whether an individual will develop CBD and/or BeS in a large cohort of beryllium-exposed individuals with a high prevalence of CBD and BeS. Methods: DNA-based typing of HLA-DP(beta)l and HLA-DR(beta)I loci at the allele level was performed on 65 CBD, 44 BeS and 288 non-effected Be-exposed age, gender and facility-matched controls. Measurements and Main Results: The DP(beta)E69 residue, particularly if present on non-*0201 alleles, was associated with both CBD and BeS. The DP(beta)DE55, 56 epitope was associated with CBD but not BeS among DP(beta)E69 positive, DP(beta)l *0201 negative subjects. The DR(beta)E71 residue was significantly increased among DP(beta)E69 negative subjects, in both CBD (1 00%), pcor = 0.045 and BeS cases (100%),pcor = 1.1x10-4 compared to controls (19.2%). DP(beta)E69 and/or DRB71 were significantly increased in CBD (100%) and in BeS subjects (100%) versus controls (50.3%), p = 7.1x10-14 and p = 2.37x10-11, respectively. DR(beta)N37 was significantly increased among DP(beta)E69 negative subjects with BeS, but residues E71, N37 and H32 in pairs, were in strong LD in both BeS and controls and therefore it is unclear as to whether any of these three residues is stronger than the other in terms of predisposing to BeS among DPPE69 negative subjects. Conclusions: Specific residues DPPE69, DRPE71 and DRPN37 influence sensitization to beryllium and the development of CBD. Our results support an interactive relationship of residues and/or genes. Some of these interactions elicit increased susceptibility while others exhibit a protective role against the development of CBD and/or BeS.
Disease-incidence; Biomarkers; Metal-compounds; Metal-fumes; Genes; Genotoxicity; Genetics; Beryllium-disease; Beryllium-compounds; Lung-disorders; Respiratory-system-disorders; Risk-factors; Surveillance-programs; Epidemiology
Kenneth D. Rosenman, Michigan State University, Department of Medicine, 117 West Fee, East Lansing, MI 48824-1315
Final Grant Report
NTIS Accession No.
Genetic/Exposure Interaction in Beryllium Disease
Michigan State University