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
Financial & competing interests disclosure
This study was supported by grants from the Spanish Health Ministry Fund for Health in Spain (FIS) network RIRAAF (RD012/0013), PI12/02247 and PI13/02598. JR Perkins is a researcher from the Sara Borrell Program (Ref CD14/00242, Carlos III National Healthy Institute, Spanish Ministry of Economy and Competitiveness). This work has been partially supported by the European Commission though the FP7 IAPP project Mr. SymBioMath (project code: 324554). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.