title: Genetic mechanism of aspirin-induced urticaria/angioedema.
abstract: OBJECTIVE
  Aspirin-induced urticaria/angioedema is a major aspirin-related hypersensitivity often associated with aspirin-intolerant asthma. Genetic studies on aspirin-intolerant asthma have shown chronic overproduction of cysteinyl leukotrienes. The genetic analysis of aspirin-induced urticaria/angioedema is limited, however.
  
  
  RESULTS
  A recent study on HLA genotypes has suggested that the HLA alleles DRB11302 and DQB10609 may be genetic markers for aspirin-induced urticaria/angioedema. A polymorphism study that examined nine single-nucleotide polymorphisms of five leukotriene-related genes [ALOX5 (encoding 5-lipoxygenase), ALOX5AP (5-lipoxygenase-activating protein), PTGS2 (cyclooxygenase 2), LTC4S (leukotriene C4 synthase), and CYSLTR1 (cysteinyl leukotriene receptor 1)] found that promoter polymorphisms of ALOX5 (-1708A>G) and CYSLTR1 (-634C>T) were significantly different between aspirin-intolerant asthma and aspirin-induced urticaria/angioedema, suggesting different contributions to the lipoxygenase pathway. A second polymorphism study, conducted on histamine-related genes, did not find any significant associations with aspirin-induced urticaria/angioedema for the genes HNMT (encoding histamine N-methyltransferase), HRH1 or HRH2 (encoding histamine receptor types 1 and 2 respectively), or the gene encoding high-affinity IgE receptor Ibeta (FcepsilonRIbeta); however, the FcepsilonRIalpha gene promoter polymorphism was significantly associated with aspirin-induced urticaria/angioedema. This finding has been supported by in vitro functional studies.
  
  
  CONCLUSIONS
  The HLA alleles DRB11302 and DQB10609, and the ALOX5 and FcepsilonRIalpha promoter polymorphisms, may contribute to the pathogenesis of aspirin-induced urticaria/angioedema. Further investigation to identify candidate genetic markers would help to elucidate the pathogenic mechanism of this condition.
authors.affiliation: Department of Allergy and Rheumatology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.forename: Soo-Keol
authors.initials: SK
authors.lastname: Lee
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000799:Angioedema / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology; D001241:Aspirin / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006632:Histamine / Q000235:genetics / Q000276:immunology; D006801:Humans; D014581:Urticaria / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006632:Histamine; D001241:Aspirin