title: HLA DRB1*15-DPB1*05 haplotype: a susceptible gene marker for isocyanate-induced occupational asthma?
abstract: BACKGROUND
  There has been no study for evaluating the associations of human leukocyte antigen (HLA) class I and II alleles with toluene diisocyanate (TDI)-induced asthma in an Asian population.
  
  
  OBJECTIVE
  The aim of this study was to investigate a susceptible or protective marker of HLA class I and II alleles in TDI-induced asthma.
  
  
  METHODS
  Fifty-five patients with TDI-induced asthma patients (group I) showing positive responses on TDI bronchoprovocation test, 47 asymptomatic exposed subjects (group II) and 95 unexposed healthy nonatopic controls (group III) were enrolled in our study. HLA class I and II genotyping was done by the direct DNA sequencing method.
  
  
  RESULTS
  The allelic frequency of C*09 (15.5%) was significantly higher in group I than in group III (6.8%, P = 0.019), but this statistical significance disappeared after correction was made for multiple comparisons. On two-locus and three-locus haplotype analysis, the allelic frequency of HLA DRB1*15-DPB1*05 in group I (10.6%) was significantly higher than that of group II (0%, P = 0.001) and group III (2.5%, P = 0.003). The allelic frequencies of HLA A*02-DRB1*15, A*02-DQB1*06, B*62-C*09 and A*02-DRB1*15-DQB1*06 were significantly higher in group I (8.5%, 10.3%, 8.2% and 6.8%, respectively) than those allelic frequencies of group III (1.3%, P = 0.002; 1.6%, P = 0.001; 0.6%, P < 0.0001; 0%, P < 0.0001, respectively). The allelic frequencies of HLA DQB1*06-DPB1*05 and DRB1*15-DQB1*06-DPB1*05 were significantly higher in group I (16.0% and 10.5%) than those in group II (2.5%, P = 0.001; 0%, P = 0.001), while the frequencies of DRB1*09-DPB1*05 and DRB1*09-DQB1*0303-DPB1*05 were significantly lower in group I (0% and 0%) than those of group II (7.4%, P = 0.004; 7.5%, P = 0.004). These differences remained statistically significant even after the correction for multiple comparisons.
  
  
  CONCLUSIONS
  The HLA haplotype DRB1*15-DPB1*05 can be a susceptibility gene marker for the development of TDI-induced asthma among the exposed workers in the Korean population.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: H-B
authors.initials: HB
authors.lastname: Oh
authors.forename: K-W
authors.initials: KW
authors.lastname: Lee
authors.forename: E-S
authors.initials: ES
authors.lastname: Shin
authors.forename: C-W
authors.initials: CW
authors.lastname: Kim
authors.forename: C-S
authors.initials: CS
authors.lastname: Hong
authors.forename: D-H
authors.initials: DH
authors.lastname: Nahm
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced / Q000235:genetics*; D015415:Biomarkers; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D006682:HLA-DP Antigens / Q000235:genetics*; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007723:Korea; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics*; D016273:Occupational Exposure / Q000009:adverse effects; D012882:Skin Tests; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D016085:Bronchoconstrictor Agents; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate