Toll-like receptor 4 polymorphism and severity of atopy in asthmatics
Toll-like receptor 4 polymorphism and severity of atopy in asthmatics
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DOI：
10.1038/sj.gene.6364037
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发表时间：
2004
影响因子：
5
通讯作者：
I. Yang;S. J. Barton;S. Rorke;J. Cakebread;T. Keith;J B Clough;S. Holgate;J. W. Holloway
中科院分区：
文献类型：
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作者：
I. Yang;S. J. Barton;S. Rorke;J. Cakebread;T. Keith;J B Clough;S. Holgate;J. W. Holloway
内毒素暴露可能对哮喘和特应性有保护作用。Toll样受体4（TLR 4）基因Asp 299 Gly多态性降低了对内毒素的反应性。本研究确定了TLR 4多态性对哮喘和特应性的风险和严重程度的影响。总共有336个英国白人家族有≥ 2个受影响的同胞（医生诊断为哮喘和当前药物使用）和179个白人没有哮喘或有哮喘家族史，使用ARMS-PCR进行基因分型。无论是在父母影响的兄弟姐妹三人组中，还是在病例对照分析中，均未发现TLR 4基因多态性与发生哮喘的风险相关（P> 0.05）。在第一个受影响的哮喘兄弟姐妹中，具有Asp/Gly或Gly/Gly基因型的患者的特应性严重程度评分（基于阳性皮肤点刺试验和特异性IgE的大小和数量）（平均值1.8，sd 1.1，n= 39）高于具有Asp/Asp基因型的患者（平均值1.2，sd 1.0，n= 279）（P= 0.003，t检验）。与总IgE、FEV1%预测值、FEV 1对乙酰甲胆碱反应的斜率及哮喘严重程度评分无相关性（P> 0.05）。这项研究证实了以前观察到的TLR 4多态性与哮喘缺乏关联。相反，研究结果表明，遗传决定的低反应性内毒素可能会增加过敏的严重程度。
Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy. In all, 336 UK Caucasian families with≥ 2 affected sibs (physician's diagnosis of asthma and current medication use) and 179 Caucasians without asthma or a family history of asthma were genotyped using ARMS-PCR. No association of the TLR4 polymorphism was found with the risk of developing asthma, either in parent-affected sibling trios, or in case–control analyses (P> 0.05). In the first affected asthmatic siblings, the atopy severity score (based on size and number of positive skin-prick tests and specific IgE) was higher in those with the Asp/Gly or Gly/Gly genotypes (mean 1.8, sd 1.1, n= 39) compared to those with the Asp/Asp genotype (mean 1.2, sd 1.0, n= 279)(P= 0.003, t-test). No associations were found with total IgE, FEV 1% predicted, slope of FEV 1 response to methacholine or asthma severity score (P> 0.05). This study confirms the previously observed lack of association of TLR4 polymorphisms with asthma. In contrast, the findings suggest that genetically determined hyporesponsiveness to endotoxin may increase atopy severity.