The HLA DRB1*1501-DQB1*0602-DPB1*0501 Haplotype Is a Risk Factor for Toluene Diisocyanate-Induced Occupational Asthma

Abstract

Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497–13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236–22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540–13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.