Smit Lidwien A M, Siroux Valérie, Bouzigon Emmanuelle, Oryszczyn Marie-Pierre, Lathrop Mark, Demenais Florence, Kauffmann Francine
INSERM U780, Villejuif, France.
Am J Respir Crit Care Med. 2009 Mar 1;179(5):363-8. doi: 10.1164/rccm.200810-1533OC. Epub 2008 Dec 18.
It has been shown that country living protects against asthma, which may be explained by microbial exposures.
To study whether single nucleotide polymorphisms (SNPs) in CD14 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.
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.
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).
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.
研究表明，乡村生活可预防哮喘，这可能与微生物接触有关。
研究CD14、Toll样受体（TLR）2、TLR4和TLR9基因中的单核苷酸多态性（SNP）是否与成人哮喘相关，以及这些SNP是否会改变乡村生活与哮喘之间的关联。
在法国哮喘、支气管高反应性和特应性的遗传学与环境流行病学研究（EGEA）的成年受试者中，对CD14、TLR2、TLR4和TLR9基因中的25个SNP进行基因分型。我们对无亲缘关系的受试者（239例哮喘患者和596例非哮喘患者）进行了病例对照分析，并在通过哮喘先证者确定的192个家庭中进行了基于家系的关联测试（FBAT）。
在病例对照分析和基于家系的分析中，TLR2 / +596 C等位基因均与哮喘风险增加相关（显性模型下，优势比[OR]为1.91，95%置信区间[CI]为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，CD14 / -260 C等位基因与哮喘呈负相关（加性模型，OR 0.66；CI 0.48 - 0.91）。发现CD14和TLR基因变异与儿童时期乡村生活之间存在显著的基因 - 环境相互作用，涉及10个SNP。在携带CD14 / -260 CC的SPT阳性受试者中，乡村生活可预防哮喘（OR为0.32；95% CI为0.12 - 0.85），而在特应性且携带CD14 / -260 T的受试者中，乡村生活与哮喘无关（OR为1.11；95% CI为0.65 - 1.90）（基因 - 环境相互作用，P < 0.05）。
TLR2和CD14的SNP分别与哮喘和特应性哮喘相关。此外，CD14、TLR2、TLR4和TLR9的SNP改变了乡村生活与哮喘之间的关联。
