The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype is a risk factor for toluene diisocyanate-induced occupational asthma.
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.


CONCLUSIONS
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.
Choi
Jeong-Hee
JH
Department of Internal Medicine, Hallym University, Anyang, Korea.
Lee
Kyung-Wha
KW
Kim
Cheol-Woo
CW
Park
Choon-Sik
CS
Lee
Hyun-Young
HY
Hur
Gyu-Young
GY
Kim
Seung-Hyun
SH
Hong
Chein-Soo
CS
Jang
An-Soo
AS
Park
Hae-Sim
HS
D000328:Adult; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007723:Korea; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects* / Q000276:immunology
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C538744:HLA-DPB1*05:01 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D008562:Membrane Glycoproteins; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E