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Transforming growth factor-beta(2) polymorphisms are associated with childhood atopic asthma.

机译:转化生长因子-β(2)多态性与儿童特应性哮喘有关。

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BACKGROUND: Transforming growth factor (TGF)-beta plays an important role in the regulation of airway inflammation and remodelling in asthma. Recent studies suggest that TGF-beta(2) is a predominant isoform expressed in severe asthma and it is also associated with airway remodelling. OBJECTIVE: To determine whether the polymorphisms in TGF-beta(2) are associated with childhood atopic bronchial asthma in a Japanese population. METHODS: We identified a total of eight polymorphisms and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants in the promoter and 3'UTR were genotyped, and we conducted an association study of TGF-beta(2) (childhood atopic asthma n=297, normal controls n=555). An association analysis of these variants and an expression and functional analysis were performed. RESULTS: 3'UTR 94862T >A was found to be significantly associated with the risk of childhood atopic asthma (P=0.00041). The -109-->ACAA ins promoter variant was also associated with the risk of childhood atopic asthma (P=0.0037). TGF-beta(2) expression was observed in both the normal and asthmatic bronchial epithelium, and both real-time PCR and an ELISA showed a significant basal and TGF-beta(1)-induced TGF-beta(2) expression in the bronchial epithelial cell line BEAS2B. Furthermore, the promoter variant -109-->ACAA ins increased the TGF-beta(2) promoter-reporter activity in BEAS2B cells. CONCLUSIONS: Our data suggest that TGF-beta(2) may therefore be involved in the development of childhood atopic asthma by means of functional genetic polymorphism. The polymorphisms in TGF-beta(2) may become important information for asthma susceptibility in children.
机译:背景:转化生长因子(TGF)-β在哮喘气道炎症和重塑中起着重要作用。最近的研究表明,TGF-β(2)是在严重哮喘中表达的主要亚型,并且还与气道重塑有关。目的:确定TGF-beta(2)中的多态性是否与日本人群儿童期特应性支气管哮喘有关。方法:我们共鉴定了8个多态性并表征了该基因的连锁不平衡(LD)定位。对启动子和3'UTR中的三个变体进行了基因分型,我们进行了TGF-beta(2)的关联研究(儿童特应性哮喘n = 297,正常对照n = 555)。对这些变体进行关联分析,并进行表达和功能分析。结果:3'UTR 94862T> A与儿童特应性哮喘的风险显着相关(P = 0.00041)。 -109-> ACAA ins启动子变异还与儿童特应性哮喘的风险相关(P = 0.0037)。在正常和哮喘支气管上皮中均观察到TGF-beta(2)的表达,实时PCR和ELISA均显示支气管中显着的基础和TGF-beta(1)诱导的TGF-beta(2)表达上皮细胞系BEAS2B。此外,启动子变体-109-> ACAA ins增加了BEAS2B细胞中TGF-beta(2)启动子-报告子的活性。结论:我们的数据表明,TGF-beta(2)因此可能通过功能性遗传多态性参与儿童特应性哮喘的发展。 TGF-beta(2)中的多态性可能成为儿童哮喘易感性的重要信息。

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