A common haplotype of the IL-31 gene influencing gene expression is associated with nonatopic eczema.
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.
Schulz
Florian
F
Pediatric Pneumology and Immunology, Charité, Berlin, Germany.
Marenholz
Ingo
I
Fölster-Holst
Regina
R
Chen
Christiane
C
Sternjak
Alexander
A
Baumgrass
Ria
R
Esparza-Gordillo
Jorge
J
Grüber
Christoph
C
Nickel
Renate
R
Schreiber
Stefan
S
Stoll
Monika
M
Kurek
Michael
M
Rüschendorf
Franz
F
Hubner
Norbert
N
Wahn
Ulrich
U
Lee
Young-Ae
YA
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
C502187:IL31 protein, human; D007378:Interleukins