...
首页> 外文期刊>Allergy >Rare TLR2 mutations reduce TLR2 receptor function and can increase atopy risk.
【24h】

Rare TLR2 mutations reduce TLR2 receptor function and can increase atopy risk.

机译:罕见的TLR2突变会降低TLR2受体功能,并可能增加特应性风险。

获取原文
获取原文并翻译 | 示例
           

摘要

BACKGROUND: Common genetic variations in toll-like receptor 2 (TLR2), an innate pathogen recognition receptor, may influence the development of atopic diseases. So far, very little is known about the role of rare TLR2 mutations in these diseases. OBJECTIVE: We investigated the functional properties of six rare amino acid changes in TLR2 (and one amino acid change in a TLR2 pseudogene) and studied their effect on atopic sensitization and disease. METHODS: We identified rare TLR2 mutations leading to amino acid changes from databases. Functional effects of TLR2 variants were analyzed by NF-kappaB-dependent luciferase reporter assay and interleukin-8 enzyme linked immunosorbent assay in vitro. The frequency of these mutations was determined in a random sample of the general population (n = 368). Association with atopic diseases were studied in a cross sectional German study population (n = 3099). RESULTS: Three out of six mutations in the TLR2 gene altered receptor activity in vitro. Out of these, only the minor allele of R753Q occurred reasonably frequent in the German population (minor allele frequency 3%). The risk to develop atopy increased by 50% in carriers of the 753Q allele (P = 0.021) and total (P = 0.040) as well as allergen specific serum IgE levels (P = 0.011) were significantly elevated. CONCLUSION: The rare but functionally relevant mutation R753Q in TLR2 may significantly affect common conditions such as atopic sensitization in the general population.
机译:背景:先天病原体识别受体toll-like receptor 2(TLR2)的常见遗传变异可能会影响特应性疾病的发展。到目前为止,对罕见的TLR2突变在这些疾病中的作用了解甚少。目的:我们研究了TLR2中6个罕见氨基酸变化(以及TLR2假基因中1个氨基酸变化)的功能特性,并研究了它们对特应性过敏和疾病的影响。方法:我们从数据库中鉴定了导致氨基酸变化的罕见TLR2突变。通过NF-kappaB依赖的荧光素酶报告基因测定法和白介素8酶联免疫吸附法体外分析TLR2变体的功能作用。这些突变的频率是在一般人群的随机样本中确定的(n = 368)。在德国的横断面研究人群(n = 3099)中研究了与特应性疾病的关联。结果:TLR2基因的六分之三的突变在体外改变了受体的活性。在这些人群中,只有R753Q的较小等位基因在德国人群中发生得相当频繁(次要等位基因频率为3%)。 753Q等位基因携带者发生异位症的风险增加50%(P = 0.021),总过敏原(I = 0.040)以及变应原特异性血清IgE水平(P = 0.011)显着升高。结论:TLR2中罕见但功能相关的突变R753Q可能会显着影响普通人群的特应性过敏等常见情况。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号