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首页> 外文期刊>The journal of asthma >Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort
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Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort

机译：严重哮喘研究计划（SARP）队列中支气管上皮细胞和支气管肺泡灌洗中哮喘易感基因的表达

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Objective: Genome-wide association studies (GWASs) have identified genes associated with asthma, however expression of these genes in asthma-relevant tissues has not been studied. This study tested expression and correlation between GWAS-identified asthma genes and asthma or asthma severity. Methods: Correlation analyses of expression levels of GWAS-identified asthma genes and asthma-related biomarkers were performed in cells from human bronchial epithelial biopsy (BEC, n = 107) and bronchial alveolar lavage (BAL, n = 94). Results: Expression levels of asthma genes between BEC and BAL and with asthma or asthma severity were weakly correlated. The expression levels of IL18R1 were consistently higher in asthma than controls or in severe asthma than mild/moderate asthma in BEC and BAL (p < 0.05). In RAD50-IL13 region, the expression levels of RAD50, not IL4, IL5, or IL13, were positively correlated between BEC and BAL ( = 0.53, P = 4.5 x 10(-6)). The expression levels of IL13 were positively correlated with IL5 in BEC ( = 0.35, P = 1.9 x 10(-4)) and IL4 in BAL ( = 0.42, P = 2.5 x 10(-5)), respectively. rs3798134 in RAD50, a GWAS-identified SNP, was correlated with IL13 expression and the expression levels of IL13 were correlated with asthma (P = 0.03). rs17772583 in RAD50 was significantly correlated with RAD50 expression in BAL and BEC (P = 7.4 x 10(-7) and 0.04) but was not associated with asthma. Conclusions: This is the first report studying the expression of GWAS-identified asthma genes in BEC and BAL. IL13, rather than RAD50, IL4, or IL5, is more likely to be the asthma susceptibility gene. Our study illustrates tissue-specific expression of asthma-related genes. Therefore, whenever possible, disease-relevant tissues should be used for transcription analysis.
机译：目的：全基因组关联研究（GWASs）已鉴定出与哮喘相关的基因，但是尚未研究这些基因在哮喘相关组织中的表达。这项研究测试了GWAS鉴定的哮喘基因与哮喘或哮喘严重程度之间的表达及其相关性。方法：在人支气管上皮活检（BEC，n = 107）和支气管肺泡灌洗（BAL，n = 94）的细胞中进行了GWAS鉴定的哮喘基因和哮喘相关生物标志物表达水平的相关性分析。结果：BEC和BAL之间的哮喘基因表达水平与哮喘或哮喘严重程度之间存在弱相关性。在BEC和BAL中，哮喘中IL18R1的表达水平始终高于对照组或重度哮喘，高于轻度/中度哮喘（p <0.05）。在RAD50-IL13区域中，BEC和BAL之间的RAD50的表达水平与IL4，IL5或IL13呈正相关（= 0.53，P = 4.5 x 10（-6））。 IL13的表达水平与BEC中的IL5（= 0.35，P = 1.9 x 10（-4））和BAL中的IL4（= 0.42，P = 2.5 x 10（-5））呈正相关。 RAD50（一种经GWAS鉴定的SNP）中的rs3798134与IL13表达相关，而IL13的表达水平与哮喘相关（P = 0.03）。 RAD50中的rs17772583与BAL和BEC中RAD50的表达显着相关（P = 7.4 x 10（-7）和0.04），但与哮喘无关。结论：这是第一份研究GWAS鉴定的哮喘基因在BEC和BAL中表达的报道。 IL13而非RAD50，IL4或IL5更可能是哮喘易感基因。我们的研究阐明了哮喘相关基因的组织特异性表达。因此，只要有可能，应使用与疾病相关的组织进行转录分析。

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