title: The human leucocyte antigen-DRB1*1302-DQB1*0609-DPB1*0201 haplotype may be a strong genetic marker for aspirin-induced urticaria.
abstract: BACKGROUND
  Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood.
  
  
  OBJECTIVE
  In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirin-intolerant asthma and normal control in a Korean population.
  
  
  METHODS
  Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine-aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis.
  
  
  RESULTS
  The allele frequencies of HLA-DRB1(*)1302 (18.1%) and HLA-DQB1(*)0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P=0.0004; 2.0%, P=0.0024) and in normal controls (8.1%, P=0.0005; 3.2%, P=0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P>0.05, respectively). In haplotype analysis, the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P=0.0014) and normal controls (2.0%, P=0.0006).
  
  
  CONCLUSIONS
  These findings suggest that the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University Hospital, Suwon 442-749, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Choi
authors.forename: K-W
authors.initials: KW
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: E-S
authors.initials: ES
authors.lastname: Shin
authors.forename: H-B
authors.initials: HB
authors.lastname: Oh
authors.forename: C-H
authors.initials: CH
authors.lastname: Suh
authors.forename: D-H
authors.initials: DH
authors.lastname: Nahm
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; 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; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D014581:Urticaria / Q000139:chemically induced* / Q000235:genetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005819:Genetic Markers; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D001241:Aspirin