Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial pathogenesis and increasing incidence in the Western world. A genetically determined defective function of pattern recognition receptors such as toll-like receptors (TLRs) has been proposed as a candidate mechanism in the pathogenesis of AD.


OBJECTIVE
To study the impact of genetic predisposition of five genes encoding for pattern recognition-related molecules for the phenotype of AD.


METHODS
We examined nine different single-nucleotide polymorphism (SNP) frequencies in the genes encoding TLR1, -2, -4, -9 and the adapter molecule TIRAP by PCR with subsequent melting curve analysis in a case/control cohort of 136 adult AD patients and 129 age and gender matched non-atopic, healthy individuals. TLR2-expression and -function in cells from genotyped individuals were analysed.


RESULTS
For the SNPs examined, similar genotype frequencies were found in both groups. In a subgroup of patients suffering from severe AD (SCORAD >50), a significantly increased representation of the A-allele in position -16934 of the tlr2 gene was present (P = 0.004). Constitutive tlr2 mRNA expression in peripheral monocytes was independent of this tlr2 promoter SNP. Stimulation assays indicated that IL-6, but not TNF-alpha secretion following TLR2 stimulation is reduced in homozygous tlr2-16934-A allele carriers.


CONCLUSIONS
These data indicate that TLR2 is relevant for the phenotype of severe AD in adults.
Oh
D-Y
DY
Institut für Mikrobiologie und Hygiene, Allergie-Centrum-Charité, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Schumann
R R
RR
Hamann
L
L
Neumann
K
K
Worm
M
M
Heine
G
G
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000235:genetics*
D015850:Interleukin-6; D051195:Toll-Like Receptor 2