An association of TLR2–16934A >T polymorphism and severity/phenotype of atopic dermatitis.
BACKGROUND
Toll-like receptor 2 gene (TLR2) –16934A>T polymorphism has been shown to be associated with severity of atopic dermatitis (AD) as measured using severity scoring of atopic dermatitis (SCORAD) index. Moreover, TLR2–16934A>T polymorphism has been associated with atopy and allergic disorders in farmers’ children.


OBJECTIVE
The aim of this study was to evaluate an association between TLR2–16934A>T polymorphism and AD phenotype, including disease severity and concomitant atopic diseases, or potential serum markers of AD severity and also to find a molecular background of the clinical associations.


METHODS
Genotyping for TLR2–16934A>T polymorphism was performed in 130 consecutive adult ambulatory patients with AD. Total serum (TS) IgE levels, serum tryptase, plasma interleukin-6 and C-reactive protein were measured. In addition, luciferase assay and electrophoretic-mobility shift assay were conducted to assess the effect of –16934A>T polymorphism on transcriptional activity.


RESULTS
There was an inverse association of TLR2–16934TT genotype and/or –16934T allele with SCORAD, but not with TS IgE, tryptase or inflammatory markers. Interestingly, –16934AA genotype and/or –16934A allele were overrepresented in AD patients with concomitant asthma or a family history of atopy. In a subgroup analysis, TLR2–16934A>T polymorphism was associated with SCORAD, asthma, allergic conjunctivitis or family history of atopy in AD patients with TS IgE ≥106 IU/mL but not in those having TS IgE <106 IU/mL. Functional analyses showed that TLR2–16934T allele is associated with higher luciferase activity in human monocytic THP-1 cells and preferential binding of the THP-1-derived nuclear protein.


CONCLUSIONS
TLR2–16934A>T polymorphism could be a genetic predictor of AD severity, the coexistence of asthma or atopic conjunctivitis as well as a family history of atopic diseases, especially in subjects having higher TS IgE. TLR2–16934A>T polymorphism affects transcriptional activity, which may at least in part account for the clinical associations observed for the –16934A>T polymorphism.
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
D P
DP
Potaczek
M
M
Nastalek
K
K
Okumura
A
A
Wojas-Pelc
A
A
Undas
C
C
Nishiyama
D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D014158:Transcription, Genetic; D053802:Tryptases / Q000097:blood
D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D007073:Immunoglobulin E; D002097:C-Reactive Protein; D053802:Tryptases