An association study of asthma and total serum immunoglobin E levels for Toll‐like receptor polymorphisms in a Japanese population

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Abstract
Summary: Background The prevalence of atopic diseases has been increasing in developed countries. This could be explained by the hygiene hypothesis, which states that exposure to specific infections or endotoxins during infancy drives the maturing immune system towards a Th1 phenotype and away from the Th2 phenotype, which is associated with allergic diseases. Toll‐like receptors (TLRs) play important roles in the signalling of many pathogen‐related molecules and endogenous proteins associated with immune activation.Objective The aim of the present study was to investigate whether polymorphisms in genes encoding TLRs are associated with asthma or total serum IgE levels.Methods We screened the 5′ flanking and coding regions of the TLR2,TLR3, TLR4, and TLR9 genes for polymorphisms by direct sequencing of DNA from 32 asthmatics, and analysed the effect of the polymorphisms on the development of atopic asthma and on total serum IgE levels.Results We identified 16 variants in TLRs. The transmission disequilibrium test of the families revealed that none of the alleles or haplotypes were associated with asthma or total IgE levels (P>0.05). However, we found an insertion/deletion polymorphism in the 5′ untranslated region of TLR2, and an expression construct containing the deletion allele showed lower luciferase activity than the wild‐type alleles, suggesting that the deletion allele has reduced transcriptional activity.Conclusion Our results indicate that polymorphisms in TLRs are not likely to be associated with the development of atopy‐related phenotypes in a Japanese population.

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