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A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema

Item Type:Article
Title:A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema
Creators Name:Schulz, F. and Marenholz, I. and Foelster-Holst, R. and Chen, C. and Sternjak, A. and Baumgrass, R. and Esparza-Gordillo, J. and Grueber, C. and Nickel, R. and Schreiber, S. and Stoll, M. and Kurek, M. and Rueschendorf, F. and Huebner, N. and Wahn, U. and Lee, Y.A.
Abstract:BACKGROUND: IL-31 is a novel cytokine that, when overexpressed in transgenic mice, induces severe itching dermatitis resembling human eczema. OBJECTIVE: We aimed to evaluate the importance of polymorphisms in the human IL-31 gene (IL31) in the genetic susceptibility to eczema. METHODS: We sequenced the entire IL-31 gene, including the promoter region, and determined the haplotype structure. Single nucleotide polymorphisms tagging the main haplotypes were genotyped in 3 independent European populations comprising 690 affected families. An association analysis of IL31 gene variants with atopic and nonatopic eczema was performed. RESULTS: We found significant association of a common IL31 haplotype with the nonatopic type of eczema in all 3 study populations (combined P = 4.5 x 10(-5)). Analysis of PBMCs in healthy individuals revealed a strong induction IL31 mRNA expression on stimulation with anti-CD3 and anti-CD28 that was 3.8-fold higher in individuals homozygous for the risk haplotype (AA) in contrast to non-A haplotype carriers, suggesting that altered regulation of IL-31 gene expression is the disease-causing factor. CONCLUSION: Our results lend strong support to an important role of IL-31 in the pathogenesis of nonatopic eczema. CLINICAL IMPLICATIONS: This study presents the first genetic risk factor for the nonatopic type of eczema and indicates a primary role of IL-31-induced pruritus in the initiation of this disease, thus proposing a new target for the prevention and therapy of eczema.
Keywords:Eczema, Nonatopic Eczema, IL-31, Pruritus, Genetic Association, Promoter, Polymorphism, Haplotype, Gene Expression
Source:Journal of Allergy and Clinical Immunology
ISSN:0091-6749
Publisher:Elsevier (The Netherlands)
Volume:120
Number:5
Page Range:1097-1102
Date:November 2007
Additional Information:The original publication is available at www.sciencedirect.com
Official Publication:https://doi.org/10.1016/j.jaci.2007.07.065
PubMed:View item in PubMed

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