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. Conclusion 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.