Genetic variants in arachidonic acid pathway genes associated with NSAID-exacerbated respiratory disease

Pharmacogenomics. 2015 Jul;16(8):825-39. doi: 10.2217/pgs.15.43. Epub 2015 Jun 12.

Abstract

Aim: 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.

Patients & 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).

Conclusion: 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.

Keywords: NSAID-exacerbated respiratory disease; NSAIDs; copy number variations; hypersensitivity drug reactions; polymorphisms.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity
  • Arachidonate 15-Lipoxygenase / genetics*
  • Arachidonic Acid / genetics*
  • Arachidonic Acid / metabolism
  • Asthma, Aspirin-Induced / genetics*
  • Asthma, Aspirin-Induced / pathology
  • Cyclooxygenase 1 / genetics*
  • Drug Hypersensitivity / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Male
  • Metabolic Networks and Pathways
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Arachidonic Acid
  • ALOX15 protein, human
  • Arachidonate 15-Lipoxygenase
  • Cyclooxygenase 1
  • PTGS1 protein, human