title: Genetic variants in arachidonic acid pathway genes associated with NSAID-exacerbated respiratory disease.
abstract: OBJECTIVE
  NSAIDs are the most frequent cause of hypersensitivity drug reactions. We have examined the association between NSAID-exacerbated respiratory disease (NERD) and genetic variants in arachidonic acid metabolism genes.
  
  
  METHODS
  We included 250 NERD patients, 260 NSAID-tolerant asthmatic (NTA) subjects and 315 healthy controls.
  
  
  RESULTS
  Significant associations with NERD were identified for: ALOX15 rs3892408 C/C homozygous genotype (NERD vs NTA; p = 0.0001, pc = 0.0011; NERD vs controls; p = 0.0001, pc = 0.0011), PTGS-1 rs5789 A/A homozygous genotype (NERD vs NTA; p = 0.0001, pc = 0.0011; NERD vs controls; p = 0.0001, pc = 0.0011), PTGS-1 rs10306135 A/A homozygous genotype (NERD vs NTA; p = 0.0009, pc = 0.0091; NERD vs controls; p = 0.0064, pc = 0.045). Differences in ALOX5 copy number variations were also found (NERD vs NTA; p = 0.010; NERD vs controls; p = 0.0001).
  
  
  CONCLUSIONS
  These results improve our understanding of the underlying mechanisms of NERD and may help develop a predictive test for this pathology. Original submitted 3 November 2014; Revision submitted 2 April 2015.
authors.affiliation: Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.|Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.affiliation: Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.|Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Plaza-Serón
authors.affiliation: Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
authors.affiliation: Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Doña
authors.affiliation: Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Campo
authors.affiliation: Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.affiliation: Allergy Service, Cruz Roja Central Hospital, Madrid, Spain.
authors.forename: José Julio
authors.initials: JJ
authors.lastname: Laguna
authors.affiliation: Allergy Unit, Pneumology & Allergy Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bartra
authors.affiliation: Allergy Service, Alicante General Hospital, Alicante, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Soriano-Gomis
authors.affiliation: Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.|Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Cornejo-García
authors.affiliation: Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000633:toxicity; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D016718:Arachidonic Acid / Q000235:genetics* / Q000378:metabolism; D055963:Asthma, Aspirin-Induced / Q000235:genetics* / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000235:genetics*; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human
keywords: NSAID-exacerbated respiratory disease; NSAIDs; copy number variations; hypersensitivity drug reactions; polymorphisms