AbstractBackgroundSeveral case‐control studies have found an association between chronic beryllium disease (CBD) and HLA‐DPB1 gene variants. However, the relationship between HLA‐DPB1 and beryllium sensitization, and whether the presence of one or two HLA‐DPB1Glu69 alleles is differentially associated with CBD and beryllium sensitization have not been completely resolved.MethodsRestriction fragment length polymorphism (RFLP) analysis was used to address these questions in a large population‐based cohort consisting of 884 beryllium workers (90 with CBD, 64 beryllium sensitized).ResultsHLA‐DPB1Glu69 was associated with both CBD (OR = 9.4; 95% CI = 5.4, 16.6) and sensitization (OR = 3.3, 95% CI = 1.9, 5.9). Further, workers with CBD and sensitization were more likely to be homozygous HLA‐DPB1Glu69 compared to workers without disease or sensitization (P < 0.001).ConclusionsFollow‐up of this cohort, scrutiny of HLA‐DPB1 haplotypes, and evaluation of gene–environment and gene–gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease. Am. J. Ind. Med. 46:95–103, 2004. Published 2004 Wiley‐Liss, Inc.