{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T13:40:07Z","timestamp":1741268407450,"version":"3.38.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Background Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti-inflammatory drugs. The pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration.<\/jats:p><jats:p>Objectives To investigate the genetic contribution of interleukin (IL)-18, which can amplify acute inflammation by promoting mast cell activation, neutrophil migration and cytokine production, to the pathogenesis of AIU.<\/jats:p><jats:p>Methods A case\u2013control association study was performed using 275 patients with AIU and 196 normal healthy controls in a Korean population. Two promoter polymorphisms of the IL18 gene (\u2212607A\/C and \u2212137G\/C) were genotyped using the primer extension method. The functional effect of the IL18 gene promoter polymorphism was investigated through in vitro studies including a luciferase reporter assay and electrophoretic mobility shift assays (EMSAs) and ex vivo studies involving neutrophil chemotaxis assays.<\/jats:p><jats:p>Results A significant association was detected between both AIU in general and the aspirin-intolerant acute urticaria (AIAU) phenotype and the IL18 promoter polymorphism \u2212607A\/C. Patients with AIAU showed higher frequencies of the C\u2212607G\u2212137 haplotype, ht1 [CG], compared with controls (P =0\u00b702). Moreover, ht1 [CG] showed a high transcript haplotype by the luciferase activity assay, and EMSAs identified a \u2212607C allele-specific DNA-binding protein as CREB2. Neutrophil chemotactic activity was highest in subjects with AIU exhibiting the high transcript haplotype, ht1 [CG] (P =0\u00b7019).<\/jats:p><jats:p>Conclusions The high transcript haplotype ht1 [CG] of the IL18 gene may contribute to the development of acute cutaneous inflammation sensitive to aspirin, leading to the clinical presentation of AIAU.<\/jats:p>","DOI":"10.1111\/j.1365-2133.2011.10467.x","type":"journal-article","created":{"date-parts":[[2011,6,21]],"date-time":"2011-06-21T12:31:39Z","timestamp":1308659499000},"page":"976-984","source":"Crossref","is-referenced-by-count":23,"title":["A functional promoter polymorphism of the human<i>IL18<\/i>gene is associated with aspirin-induced urticaria"],"prefix":"10.1093","volume":"165","author":[{"given":"S-H.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon 442-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.K.","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon 442-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E-M.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon 442-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-E.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon 442-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-S.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical 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