title: A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema.
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.
  
  
  CONCLUSIONS
  Our results lend strong support to an important role of IL-31 in the pathogenesis of nonatopic eczema.
  
  
  CONCLUSIONS
  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.
authors: Pediatric Pneumology and Immunology, Charité, Berlin, Germany.
authors: Florian
authors: F
authors: Schulz
authors: Ingo
authors: I
authors: Marenholz
authors: Regina
authors: R
authors: Fölster-Holst
authors: Christiane
authors: C
authors: Chen
authors: Alexander
authors: A
authors: Sternjak
authors: Ria
authors: R
authors: Baumgrass
authors: Jorge
authors: J
authors: Esparza-Gordillo
authors: Christoph
authors: C
authors: Grüber
authors: Renate
authors: R
authors: Nickel
authors: Stefan
authors: S
authors: Schreiber
authors: Monika
authors: M
authors: Stoll
authors: Michael
authors: M
authors: Kurek
authors: Franz
authors: F
authors: Rüschendorf
authors: Norbert
authors: N
authors: Hubner
authors: Ulrich
authors: U
authors: Wahn
authors: Young-Ae
authors: YA
authors: Lee
mesh_terms: D000328:Adult; D002648:Child; D004485:Eczema / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000235:genetics*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C502187:IL31 protein, human; D007378:Interleukins