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

Abstract

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.

• Authors: D P Potaczek, M Nastalek, K Okumura, A Wojas-Pelc, A Undas, C Nishiyama
• Journal: Journal of the European Academy of Dermatology and Venereology : JEADV (J Eur Acad Dermatol Venereol) Vol. 25 Issue 6 Pg. 715-21 (Jun 2011) ISSN: 1468-3083 [Electronic] England
• PMID: 21134221 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Toll-Like Receptor 2
• Immunoglobulin E
• C-Reactive Protein
• Tryptases

Topics

• Adult
• Alleles
• Asthma (genetics)
• C-Reactive Protein (metabolism)
• Dermatitis, Atopic (blood, genetics)
• Female
• Genotype
• Humans
• Immunoglobulin E (blood)
• Interleukin-6 (blood)
• Male
• Phenotype
• Polymorphism, Genetic (genetics)
• Severity of Illness Index
• Toll-Like Receptor 2 (genetics)
• Transcription, Genetic
• Tryptases (blood)