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2015•PharmacogenomicsOpen access

Genetic Variants in Arachidonic Acid Pathway Genes Associated with NSAID-Exacerbated Respiratory Disease

Pedro Ayuso, María del Carmen Plaza‐Seron, Natalia Blanca‐López, Inmaculada Doña, Paloma Campo, Gabriela Cantó, José Julio Laguna, Joan Bartra, Víctor Soriano, Miguel Blanca, José Antonio Cornejo-García, James Richard Perkins

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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.

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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.

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Available 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.

Key concepts: Nerd, Medicine, Genotype, Internal medicine, Gastroenterology, Arachidonic acid, Disease, Reflux

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