title: The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively).
  
  
  CONCLUSIONS
  The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.
authors.affiliation: Departamento de Farmacología, Universidad de Extremadura, Cáceres, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.forename: José A
authors.initials: JA
authors.lastname: Cornejo-García
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: María J
authors.initials: MJ
authors.lastname: Torres
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Doña
authors.forename: María
authors.initials: M
authors.lastname: Salas
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
authors.forename: Carmen
authors.initials: C
authors.lastname: Rondon
authors.forename: Paloma
authors.initials: P
authors.lastname: Campo
authors.forename: José J
authors.initials: JJ
authors.lastname: Laguna
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics* / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007073:Immunoglobulin E; D006631:Amine Oxidase (Copper-Containing)