title: Copy number variation in ALOX5 and PTGER1 is associated with NSAIDs-induced urticaria and/or angioedema.
abstract: Cross-intolerance to NSAIDs is a class of drug hypersensitivity reaction, of which NSAIDs-induced urticaria and/or angioedema (NIUA) are the most frequent clinical entities. They are considered to involve dysregulation of the arachidonic acid pathway; however, this mechanism has not been confirmed for NIUA. In this work, we assessed copy number variations (CNVs) in eight of the main genes involved in the arachidonic acid pathway and their possible genetic association with NIUA.
  
  
  
  CNVs in ALOX5, LTC4S, PTGS1, PTGS2, PTGER1, PTGER2, PTGER3, and PTGER4 were analyzed using TaqMan copy number assays. Genotyping was carried out by real-time quantitative PCR. Individual genotypes were assigned using the CopyCaller Software. Statistical analysis was carried out using GraphPad prism 5, PLINK, EPIDAT, and R version 3.1.2.
  
  
  
  A total of 151 cases and 139 controls were analyzed during the discovery phase and 148 cases and 140 controls were used for replication. CNVs in open reading frames were found for ALOX5, PTGER1, PTGER3, and PTGER4. Statistically significant differences in the CNV frequency between NIUA and controls were found for ALOX5 (Pc=0.017) and PTGER1 (Pc=1.22E-04). This study represents the first analysis showing an association between CNVs in exonic regions of ALOX5 and PTGER1 and NIUA. This suggests a role of CNVs in this pathology that should be explored further.
authors.affiliation: aAllergy service, Infanta Leonor Hospital bResearch Unit and Biomedical Research Center in Respiratory Diseases, Carlos III Health Institute, Tenerife cAllergy Unit dResearch Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga Departments of ePharmacology fBiochemistry and Molecular Biology, University of Extremadura, Cáceres, Spain gINSERM U-954, University of Lorraine and University Hospital Center (CHU) of Nancy, Nancy, France.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Plaza-Serón
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.forename: Natalia
authors.initials: N
authors.lastname: Pérez-Sánchez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Doña
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-Lopez
authors.forename: Carlos
authors.initials: C
authors.lastname: Flores
authors.forename: Luisa
authors.initials: L
authors.lastname: Galindo
authors.forename: Ana
authors.initials: A
authors.lastname: Molina
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cornejo-García
authors.forename: Jose A
authors.initials: JA
authors.lastname: Agúndez
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: Paloma
authors.initials: P
authors.lastname: Campo
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
mesh_terms: D000328:Adult; D000799:Angioedema / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000235:genetics*; D014581:Urticaria / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C545635:PTGER1 protein, human; D058306:Receptors, Prostaglandin E, EP1 Subtype; D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human