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突尼斯儿童中Toll样受体和CD14基因多态性与哮喘易感性

Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children.

作者信息

Lachheb J, Dhifallah I B, Chelbi H, Hamzaoui K, Hamzaoui A

机构信息

Homeostasis and Cell Dysfunction Unit Research 99/UR/08-40, Medicine University of Tunis, Tunis, Tunisia.

出版信息

Tissue Antigens. 2008 May;71(5):417-25. doi: 10.1111/j.1399-0039.2008.01011.x. Epub 2008 Feb 28.

Abstract

Many studies have shown the implication of CD14 and toll-like receptors (TLRs) 2, 4 and 9 in the pathogenesis of asthma or atopy. To evaluate the association of CD14 and TLRs gene polymorphisms with asthma or atopy, 210 asthmatic children, 224 controls and 80 families were enrolled in this study. Six single nucleotide polymorphisms TLR2 (+2408 G-->A), TLR4 (+1196 C-->T), TLR4 (+896 A-->G), TLR9 (-1237 T-->C), TLR9 (-1486 T-->C) and CD14 (-159 C-->T) were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism in the case-control and family study. The -1237C allele in TLR9 gene polymorphisms was associated with increased risk of asthma [odds ratio 1.53, 95% confidence interval (1.03-2.27)], although no statistically significant differences in allele or genotype frequencies of four other TLRs polymorphisms were evident between the asthmatic and control groups. The CD14 -159 C allele was found to be significantly higher in the asthmatic group when compared with controls (P=0.0006<0.05). Transmission disequilibrium test of 80 asthmatic families showed significant transmission of the -159 C allele in the CD14 gene to asthma-affected offspring. It was concluded that TLR9 and CD14 gene polymorphisms may contribute to an inherited predisposition to asthma in Tunisian children.

摘要

许多研究表明,CD14和Toll样受体(TLRs)2、4及9在哮喘或特应性疾病的发病机制中具有重要作用。为评估CD14和TLRs基因多态性与哮喘或特应性疾病的关联,本研究纳入了210名哮喘儿童、224名对照儿童及80个家庭。采用聚合酶链反应(PCR)结合限制性片段长度多态性方法,对TLR2(+2408 G→A)、TLR4(+1196 C→T)、TLR4(+896 A→G)、TLR9(-1237 T→C)、TLR9(-1486 T→C)和CD14(-159 C→T)这6个单核苷酸多态性位点进行基因分型,开展病例对照研究及家系研究。TLR9基因多态性中的-1237C等位基因与哮喘风险增加相关[比值比1.53,95%置信区间(1.03 - 2.27)],尽管哮喘组与对照组在其他4种TLRs多态性的等位基因或基因型频率上未发现统计学显著差异。与对照组相比,哮喘组的CD14 -159 C等位基因频率显著更高(P = 0.0006 < 0.05)。对80个哮喘家系进行传递不平衡检验发现,CD14基因中的-159 C等位基因显著传递给了受哮喘影响的后代。研究得出结论,TLR9和CD14基因多态性可能在突尼斯儿童哮喘的遗传易感性中发挥作用。

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