Department of Respiratory Medicine, QiLu Children's hospital of Shandong university, Jinan, Shandong, China.
PLoS One. 2013;8(2):e56914. doi: 10.1371/journal.pone.0056914. Epub 2013 Feb 22.
Previous studies have demonstrated that integrins are involved in the aetiology of asthma. Several single-nucleotide polymorphisms (SNPs) in the integrin β3 (ITGB3) gene are significantly associated with asthma in Western populations. Given the important roles of environmental exposures in the development of asthma, we evaluated the associations between six SNPs in ITGB3 and asthma in Chinese Han children. A total of 321 unrelated Chinese children with asthma and 315 healthy children were recruited for the study. SNP genotyping was performed by high-resolution melting analysis (HRM). The selected SNPs were well genotyped by HRM, and SNP rs3809865 in the 3' untranslated region (3'UTR) of ITGB3 was found to be strongly associated with asthma (adjusted p = 0.004). The minor allele of rs3809865 showed a protective effect against asthma (OR: 0.59; 95% CI: 0.43-0.8). The seed regions of two miRNAs (hsa-mir-124 and hsa-mir-506) were predicted to bind to the sequence containing rs3809865 by TargetScan and PITA. Luciferase reporter assays demonstrated that the T allele of rs3809865 was more efficiently targeted by hsa-mir-124 than was the A allele, which suggested that rs3809865 could affect the binding of hsa-mir-124 to ITGB3. Furthermore, the transfection of A549 cells with hsa-mir-124 resulted in the downregulation of ITGB3 expression. Our results revealed that rs3809865 was significantly associated with asthma due to its effect on the binding of hsa-mir-124 to ITGB3.
先前的研究表明整合素参与了哮喘的发病机制。在西方人群中，整合素β3（ITGB3）基因中的几个单核苷酸多态性（SNP）与哮喘显著相关。鉴于环境暴露在哮喘发展中的重要作用，我们评估了 ITGB3 中的六个 SNP 与中国汉族儿童哮喘之间的关联。共招募了 321 名无亲缘关系的哮喘患儿和 315 名健康儿童进行研究。通过高分辨率熔解分析（HRM）进行 SNP 基因分型。所选 SNP 通过 HRM 得到了很好的基因分型，并且发现 ITGB3 的 3'非翻译区（3'UTR）中的 SNP rs3809865 与哮喘强烈相关（调整后的 p = 0.004）。rs3809865 的次要等位基因对哮喘具有保护作用（OR：0.59；95%CI：0.43-0.8）。两个 miRNA（hsa-mir-124 和 hsa-mir-506）的种子区域被预测通过 TargetScan 和 PITA 与包含 rs3809865 的序列结合。荧光素酶报告基因实验表明，rs3809865 的 T 等位基因比 A 等位基因更有效地被 hsa-mir-124 靶向，这表明 rs3809865 可能影响 hsa-mir-124 与 ITGB3 的结合。此外，用 hsa-mir-124 转染 A549 细胞导致 ITGB3 表达下调。我们的研究结果表明，由于 rs3809865 影响 hsa-mir-124 与 ITGB3 的结合，因此它与哮喘显著相关。
