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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
Buscar no Google
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