title: Association study of genetic variants in PLA2G4A, PLCG1, LAT, SYK, and TNFRS11A genes in NSAIDs-induced urticaria and/or angioedema patients.
abstract: NSAIDs-induced urticaria and/or angioedema (NIUA) is the most frequent entity of hypersensitivity reactions to NSAIDs. The underlying cause is considered to be because of a nonspecific immunological mechanism in which mast cells are key players. We studied the association of nine single nucleotide polymorphisms in five genes involved in mast cell activation (SYK, LAT1, PLCG1, PLA2G4A, and TNFRSF11A) in 450 NIUA patients and 500 controls. We identified several statistically significant associations when stratifying patients by symptoms: PLA2G4A rs12746200 (urticaria vs. controls, Pc=0.005). PLCG1 rs2228246 (angioedema vs. controls; Pc=0.044), and TNFRS11A rs1805034 (urticaria+angioedema vs. controls; Pc=0.041). The frequency of haplotype PLCG1 rs753381-rs2228246 (C-G) in angioedema-NIUA patients was lower than that in controls (Pc=0.040). In addition, the haplotype frequency of TNFRS11A rs1805034-rs35211496 (C-T) was higher among urticaria-NIUA and urticaria+angioedema-NIUA patients than the controls (Pc=0.045 and 0.046). Our results shed light on the involvement of variants in genes related to non-immunological mast cell activation in NIUA.
authors.affiliation: aResearch Laboratory bAllergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Malaga cAllergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ayuso
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Plaza-Serón
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Doña
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-López
authors.forename: Paloma
authors.initials: P
authors.lastname: Campo
authors.forename: José A
authors.initials: JA
authors.lastname: Cornejo-García
authors.forename: James R
authors.initials: JR
authors.lastname: Perkins
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Torres
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.forename: Gabriela
authors.initials: G
authors.lastname: Canto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000799:Angioedema / Q000139:chemically induced* / Q000235:genetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D054513:Group IV Phospholipases A2 / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051966:Phospholipase C gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D000072377:Syk Kinase; D014581:Urticaria / Q000139:chemically induced* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047908:Intracellular Signaling Peptides and Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human; C522157:PLCG1 protein, human; D051966:Phospholipase C gamma