title: Pathogenesis of nonsteroidal antiinflammatory drug-induced asthma.
abstract: OBJECTIVE
  To summarize recent findings related to the pathogenic mechanisms of aspirin-induced asthma with emphasis on molecular genetic mechanisms.
  
  
  RESULTS
  The overproduction of cysteinyl leukotrienes with the increased expression of cysteinyl leukotriene receptor 1 (CYSLTR1) is a consistent finding in aspirin-induced asthma patients. Recent data have suggested a dysregulation of cyclooxygenase-2 and prostaglandin E2, increased levels of 15-hydroxyeicosatetranoic acid, and decreased lipoxin generation as characteristics of the condition. The HLA allele DPB10301 was documented as a strong genetic marker for susceptibility in an Asian population. Leukotriene C4 synthase has been established as a key genetic determinant of aspirin-induced asthma, but recent studies have demonstrated that several single nucleotide polymorphisms in the promoters of prostaglandin E2 receptor subtype 2, CYSLTR1 and CYSLTR2 and T-box expressed in T cells (TBX21) could increase risk for the condition. Although cyclooxygenase-2 and thromboxane A2 receptor polymorphisms were not associated with aspirin-induced asthma phenotype, they may exert functional effects.
  
  
  CONCLUSIONS
  The identification of genetic markers for aspirin-induced asthma susceptibility along with in-vitro functional studies would help to elucidate the pathogenesis of the condition. Further studies of the interactions among genes and between genes and the environment will be essential.
authors.affiliation: Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin