SummaryBackground 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 aspirinintolerant 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 5 0.0004; 2.0%, P 5 0.0024) and in normal controls (8.1%, P 5 0.0005; 3.2%, P 5 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 (P40.05, 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 5 0.0014) and normal controls (2.0%, P 5 0.0006). Conclusion 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.
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