Common human Toll-like receptor 9 polymorphisms and haplotypes:: association with atopy and functional relevance
Common human Toll-like receptor 9 polymorphisms and haplotypes:: association with atopy and functional relevance
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DOI：
10.1111/j.1365-2222.2005.02325.x
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发表时间：
2005-09-01
影响因子：
6.1
通讯作者：
Hackstein, H
中科院分区：
文献类型：
--
作者：
Berghöfer, B;Frommer, T;Hackstein, H
背景Toll样受体9(TLR9)是一种模式识别受体，检测细菌和病毒DNA中普遍存在的未甲基化的CpG基序。TLR9刺激是细菌感染后的一个关键事件，触发先天免疫和T辅助细胞1型偏斜的获得性免疫。合成的CpG-寡核苷酸(CpG-ODN)代表着一类很有前途的新型免疫佐剂，用于变态反应治疗、疫苗接种和癌症治疗。然而，常见的功能性TLR9基因变异会干扰CpG-ODN在免疫治疗中的临床应用。目的探讨TLR9基因C-1237T多态和单倍型是否具有功能相关性以及与特应性疾病的关系。方法对527例健康献血员的TLR9基因启动子、外显子和内含子区域5个常见的单核苷酸多态(SNPs)进行基因分型，并估算4种常见单倍型。检测总IgE和抗最常见空气变应原的特异性IgE水平(n=303)。用TLR9配体CpG-ODN(n=220)刺激浆细胞样树突状细胞(PDC)产生干扰素-α。结果TLR9常见多态和单倍型对总IgE水平和特异性IgE水平无显著影响。CpG-ODN诱导的干扰素-α的功能分析未发现常见的TLR9基因多态性在TLR9功能中的显著作用。结论TLR9基因的共同遗传差异对变态反应易感性没有重大影响，对CpG-ODN的临床应用不太可能产生影响。
Background Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported.Objective The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy.Methods We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220).Results No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function.Conclusion We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.