Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma
Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma
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DOI：
10.1007/s10038-004-0161-4
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Tamari, M
中科院分区：
文献类型：
--
作者：
Hirota, T;Obara, K;Tamari, M
肺上皮细胞在调节肺部炎症反应中起着重要作用，肺修复和气道上皮细胞是哮喘和病毒感染的靶点。活化的T淋巴细胞释放细胞因子，例如干扰素-γ（IFN-γ），其诱导受损上皮细胞的凋亡或程序性细胞死亡。死亡相关蛋白3（DAP 3）参与介导IFN-γ诱导的细胞死亡。为了评估DAP 3基因变异与哮喘的可能关系，我们寻找了该基因的单核苷酸多态性（SNPs），并对1,341名受试者进行了病例对照研究。我们发现成人支气管哮喘（BA）之间存在强相关性（P=0.0051，比值比=1.87，95%CI =1.20-2.92），而未发现与儿童哮喘相关。血清总免疫球蛋白E（IgE）>250 IU/ml的患者，这种趋势更明显（P=0.00061，OR =2.40，95% CI=1.44-4.00）。DAP 3在正常支气管上皮细胞中表达，且表达受IFN-γ诱导。这些结果表明，DAP 3基因的特定变体可能与成人BA的机制有关，并有助于气道炎症和重塑。
Lung epithelium plays a central role in modulation of the lung inflammatory response, and lung repair and airway epithelial cells are targets in asthma and viral infection. Activated T lymphocytes release cytokines such as interferon-gamma (IFN-gamma) that induce apoptosis, or programmed cell death, of damaged epithelial cells. Death-associated protein-3 (DAP3) is involved in mediating IFN-gamma-induced cell death. To assess the possible involvement of genetic variants of DAP3 with asthma, we searched for single-nucleotide polymorphisms (SNPs) in the gene and conducted a case-control study with 1,341 subjects. We found a strong association between bronchial asthma (BA) in adults (P=0.0051, odds ratio=1.87, 95% CI=1.20-2.92), whereas no association was found with childhood asthma. The tendency was more prominent in patients with higher serum total immunoglobulin E (IgE) (>250 IU/ml) (P=0.00061, odds ratio=2.40, 95% CI=1.44-4.00). DAP3 was expressed in normal bronchial epithelial cells, and the expression was induced by IFN-gamma. These results indicated that specific variants of the DAP3 gene might be associated with the mechanisms responsible for adult BA and contribute to airway inflammation and remodeling.