Genetic mechanism of aspirin-induced urticaria/angioedema.

Abstract

PURPOSE OF REVIEW:

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.

RECENT FINDINGS:

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.

SUMMARY:

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: Seung-Hyun Kim, Young-Min Ye, Soo-Keol Lee, Hae-Sim Park
• Journal: Current opinion in allergy and clinical immunology (Curr Opin Allergy Clin Immunol) Vol. 6 Issue 4 Pg. 266-70 (Aug 2006) ISSN: 1528-4050 [Print] United States
• PMID: 16825866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DR Antigens
• HLA-DRB1 Chains
• Histamine
• Aspirin

Topics

• Angioedema (blood, chemically induced, genetics, immunology)
• Aspirin (adverse effects)
• Drug Hypersensitivity (etiology, genetics, immunology)
• HLA-DQ Antigens (genetics, immunology)
• HLA-DQ beta-Chains
• HLA-DR Antigens (genetics, immunology)
• HLA-DRB1 Chains
• Histamine (genetics, immunology)
• Humans
• Urticaria (chemically induced, genetics, immunology, microbiology)