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A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria.
- Source :
-
The British journal of dermatology [Br J Dermatol] 2011 Nov; Vol. 165 (5), pp. 976-84. Date of Electronic Publication: 2011 Sep 15. - Publication Year :
- 2011
-
Abstract
- 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.<br />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.<br />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.<br />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).<br />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.<br /> (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)
- Subjects :
- Adult
Case-Control Studies
Cell Movement genetics
Drug Eruptions genetics
Female
Genotype
Haplotypes
Humans
Male
Middle Aged
Promoter Regions, Genetic genetics
Transcription, Genetic genetics
U937 Cells
Young Adult
Anti-Inflammatory Agents, Non-Steroidal adverse effects
Aspirin adverse effects
Interleukin-18 genetics
Polymorphism, Single Nucleotide genetics
Urticaria chemically induced
Urticaria genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2133
- Volume :
- 165
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The British journal of dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 21692767
- Full Text :
- https://doi.org/10.1111/j.1365-2133.2011.10467.x