A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema.
J Allergy Clin Immunol
; 120(5): 1097-102, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17900679
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.
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Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Interleucinas
/
Polimorfismo de Nucleotídeo Único
/
Eczema
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Child
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article