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A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria.

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dc.contributor.authorKim, SH-
dc.contributor.authorSon, JK-
dc.contributor.authorYang, EM-
dc.contributor.authorKim, JE-
dc.contributor.authorPark, HS-
dc.date.accessioned2012-04-26-
dc.date.available2012-04-26-
dc.date.issued2011-
dc.identifier.issn0007-0963-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/6563-
dc.description.abstractBACKGROUND: 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.



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.



METHODS: A case-control 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 (-607A/C and -137G/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.



RESULTS: A significant association was detected between both AIU in general and the aspirin-intolerant acute urticaria (AIAU) phenotype and the IL18 promoter polymorphism -607A/C. Patients with AIAU showed higher frequencies of the C(-607) G(-137) haplotype, ht1 [CG], compared with controls (P=0·02). Moreover, ht1 [CG] showed a high transcript haplotype by the luciferase activity assay, and EMSAs identified a -607C allele-specific DNA-binding protein as CREB2. Neutrophil chemotactic activity was highest in subjects with AIU exhibiting the high transcript haplotype, ht1 [CG] (P=0·019).



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.
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dc.language.isoen-
dc.subject.MESHAdult-
dc.subject.MESHAnti-Inflammatory Agents, Non-Steroidal-
dc.subject.MESHAspirin-
dc.subject.MESHCase-Control Studies-
dc.subject.MESHCell Movement-
dc.subject.MESHDrug Eruptions-
dc.subject.MESHFemale-
dc.subject.MESHGenotype-
dc.subject.MESHHaplotypes-
dc.subject.MESHHumans-
dc.subject.MESHInterleukin-18-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHPolymorphism, Single Nucleotide-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHTranscription, Genetic-
dc.subject.MESHU937 Cells-
dc.subject.MESHUrticaria-
dc.subject.MESHYoung Adult-
dc.titleA functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria.-
dc.typeArticle-
dc.identifier.pmid21692767-
dc.identifier.urlhttp://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-0963&date=2011&volume=165&issue=5&spage=976-
dc.contributor.affiliatedAuthor김, 승현-
dc.contributor.affiliatedAuthor박, 해심-
dc.type.localJournal Papers-
dc.identifier.doi10.1111/j.1365-2133.2011.10467.x-
dc.citation.titleThe British journal of dermatology-
dc.citation.volume165-
dc.citation.number5-
dc.citation.date2011-
dc.citation.startPage976-
dc.citation.endPage984-
dc.identifier.bibliographicCitationThe British journal of dermatology, 165(5). : 976-984, 2011-
dc.identifier.eissn1365-2133-
dc.relation.journalidJ000070963-
Appears in Collections:
Journal Papers > Hospital > Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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