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.
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 ADpatients 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 ADpatients 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.
Authors: Melanie A Ruffner; Li Song; Kelly Maurer; Lihua Shi; Margaret C Carroll; Joshua X Wang; Amanda B Muir; Jonathan M Spergel; Kathleen E Sullivan Journal: Allergy Date: 2019-07-25 Impact factor: 13.146
Authors: Cushla McKinney; Lisa K Stamp; Nicola Dalbeth; Ruth K Topless; Richard O Day; Diluk Rw Kannangara; Kenneth M Williams; Matthijs Janssen; Timothy L Jansen; Leo A Joosten; Timothy R Radstake; Philip L Riches; Anne-Kathrin Tausche; Frederic Lioté; Alexander So; Tony R Merriman Journal: Arthritis Res Ther Date: 2015-10-13 Impact factor: 5.156
Authors: M R López-Álvarez; W Jiang; D C Jones; J Jayaraman; C Johnson; W O Cookson; M F Moffatt; J Trowsdale; J A Traherne Journal: Immunogenetics Date: 2016-06-22 Impact factor: 2.846