Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M, Arinami T
Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki-ken, Japan.
Clin Exp Allergy. 2004 Feb;34(2):177-83. doi: 10.1111/j.1365-2222.2004.01839.x.
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.
The aim of the present study was to investigate whether polymorphisms in genes encoding TLRs are associated with asthma or total serum IgE levels.
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.
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.
Our results indicate that polymorphisms in TLRs are not likely to be associated with the development of atopy-related phenotypes in a Japanese population.
在发达国家，过敏性疾病的患病率一直在上升。这可以用卫生假说解释，该假说认为婴儿期接触特定感染或内毒素会促使成熟的免疫系统向Th1表型发展，远离与过敏性疾病相关的Th2表型。Toll样受体（TLRs）在许多与病原体相关的分子以及与免疫激活相关的内源性蛋白质的信号传导中发挥重要作用。
本研究旨在调查编码TLRs的基因多态性是否与哮喘或血清总IgE水平相关。
我们通过对32名哮喘患者的DNA进行直接测序，筛查TLR2、TLR3、TLR4和TLR9基因的5'侧翼和编码区域的多态性，并分析这些多态性对过敏性哮喘发展和血清总IgE水平的影响。
我们在TLRs中鉴定出16个变异体。对这些家庭的传递不平衡测试显示，没有一个等位基因或单倍型与哮喘或总IgE水平相关（P>0.05）。然而，我们在TLR2的5'非翻译区发现了一个插入/缺失多态性，含有缺失等位基因的表达构建体显示出比野生型等位基因更低的荧光素酶活性，这表明缺失等位基因的转录活性降低。
我们的结果表明，在日本人群中，TLRs基因多态性不太可能与过敏性相关表型的发展有关。
