CD14 and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults
CD14 and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults
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DOI：
10.1164/rccm.200810-1533oc
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发表时间：
2009-03-01
影响因子：
24.7
通讯作者：
Kauffmann, Francine
中科院分区：
文献类型：
--
作者：
Smit, Lidwien A. M.;Siroux, Valerie;Kauffmann, Francine
研究表明，乡村生活可以预防哮喘，这可以通过微生物暴露来解释。目的：研究CD 14和Toll样受体（TLR）2、TLR 4和TLR 9基因的单核苷酸多态性（SNP）是否与成人哮喘相关，以及这些SNP是否改变了乡村生活与哮喘之间的关联。对来自法国哮喘遗传学和环境流行病学研究的成人受试者中CD 14、TLR 2、TLR 4和TLR 9基因中的25个SNP进行基因分型，支气管高反应性和特应性（EGEA）。我们对无关的受试者进行了病例对照分析（239例哮喘患者和596例非哮喘患者），并在192个通过哮喘先证者确定的家庭中进行基于家庭的关联试验（FBAT）。在病例对照和基于家族的分析中，TLR 2/+596 C等位基因与哮喘风险增加相关（优势模型下，比值比[OR] 1.91和95%可信区间[CI] 1.34-2.72，P = 0.0003; FBAT的Z统计量= 2.48，P = 0.01）。在皮肤点刺试验（SPT）阳性的受试者中，CD 14/-260C等位基因与哮喘呈负相关（相加模型，OR 0.66; CI 0.48-0.91）。在10个SNPs中，发现了CD 14和TLR基因变异与儿童时期农村生活之间的显著基因-环境相互作用。在携带CD 14/-260 CC的SPT阳性受试者中，乡村生活可预防哮喘（OR，0.32; 95%CI，0.12-0.85），而在特应性和携带CD 14/-260 T的受试者中，乡村生活与哮喘无关。结论：TLR 2和CD 14单核苷酸多态性分别与哮喘和特应性哮喘相关。此外，CD 14、TLR 2、TLR 4和TLR 9 SNP改变了乡村生活与哮喘之间的关联。
Rationale It has been shown that country living protects against asthma, which may be explained by microbial exposures. Objectives: To study whether single nucleotide polymorphisms (SNPs) in CD 14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma.Methods: Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma.Measurements and Main Results: The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05).Conclusions: TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma.