An association of TLR2-16934A>T polymorphism and severity/phenotype of atopic dermatitis

被引:46
作者
Potaczek, D. P. [1 ]
Nastalek, M. [2 ]
Okumura, K. [1 ,3 ]
Wojas-Pelc, A. [2 ]
Undas, A. [4 ]
Nishiyama, C. [1 ]
机构
[1] Juntendo Univ, Sch Med, Atopy Allergy Res Ctr, Tokyo 113, Japan
[2] Jagiellonian Univ, Dept Dermatol, Sch Med, Krakow, Poland
[3] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
[4] Jagiellonian Univ, Sch Med, Inst Cardiol, Krakow, Poland
基金
日本学术振兴会;
关键词
atopic dermatitis; IgE; polymorphism; SCORAD; TLR2; tryptase; TOLL-LIKE RECEPTOR-2; MAST-CELL TRYPTASE; DISEASE SEVERITY; R753Q POLYMORPHISM; PHENOTYPE; CHILDREN; FARMERS; ASTHMA; TLR2; GENE;
D O I
10.1111/j.1468-3083.2010.03812.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:715 / 721
页数:7
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