An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population
An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population
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DOI：
10.1111/j.1365-2222.2004.01839.x
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发表时间：
2004-02-01
影响因子：
6.1
通讯作者：
Arinami, T
中科院分区：
文献类型：
--
作者：
Noguchi, E;Nishimura, F;Arinami, T
背景 在发达国家，特应性疾病的患病率一直在增加。这可以用卫生假说来解释，该假说指出，婴儿期接触特定感染或内毒素会促使成熟的免疫系统转向 Th1 表型，远离与过敏性疾病相关的 Th2 表型。 Toll样受体(TLRs)在许多病原体相关分子和与免疫激活相关的内源性蛋白的信号传导中发挥着重要作用。目的本研究的目的是研究编码TLRs的基因的多态性是否与哮喘或血清总IgE水平相关。方法我们通过对来自32个基因的DNA进行直接测序来筛选TLR2、TLR3、TLR4和TLR9基因的5'侧翼和编码区的多态性。哮喘患者，并分析了多态性对特应性哮喘发展和血清总 IgE 水平的影响。结果我们鉴定了 TLR 中的 16 个变异。家系的传递不平衡测试显示，所有等位基因或单倍型均与哮喘或总IgE水平无关（P>0.05）。然而，我们在 TLR2 的 5' 非翻译区发现了插入/缺失多态性，并且包含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，表明缺失等位基因降低了转录活性。结论我们的结果表明，TLR 中的多态性不太可能与日本人群中特应性相关表型的发展相关。
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.