Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort.
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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DOI：
10.3109/02770903.2016.1158268
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Meyers DA
中科院分区：
文献类型：
--
作者：
Li X;Hawkins GA;Moore WC;Hastie AT;Ampleford EJ;Milosevic J;Li H;Busse WW;Erzurum SC;Kaminski N;Wenzel SE;Bleecker ER;Meyers DA
全基因组关联研究（GWAS）已经确定了与哮喘相关的基因，但这些基因在哮喘相关组织中的表达尚未研究。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和相关性。在来自人支气管上皮活检（BEC，n=107）和支气管肺泡灌洗（BAL，n=94）的细胞中进行GWAS鉴定的哮喘基因和哮喘相关生物标志物的表达水平的相关性分析。哮喘基因在BEC和BAL中的表达水平与哮喘及哮喘严重程度呈弱相关。哮喘组BEC和BAL中IL 18 R1的表达水平均高于对照组，重度哮喘组高于轻中度哮喘组（p<0.05）。在RAD 50-IL 13区域，BEC和BAL中RAD 50的表达水平呈正相关（rho=0.53，P=4.5×10−6），而IL 4、IL 5或IL 13的表达水平则无相关性。BEC中IL 13表达水平与IL 5（rho=0.35，P=1.9×10−4）和BAL中IL 4（rho=0.42，P=2.5×10−5）呈正相关。RAD 50中rs3798134（一个GWAS鉴定的SNP）与IL 13表达相关，IL 13表达水平与哮喘相关（P=0.03）。RAD 50中的rs 17772583与BAL和BEC中的RAD 50表达显著相关（P=7.4×10−7和0.04），但与哮喘无关。这是第一份研究GWAS鉴定的哮喘基因在BEC和BAL中表达的报告。IL 13，而不是RAD 50，IL 4或IL 5，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，只要可能，疾病相关组织应用于转录分析。
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. 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). 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 (rho=0.53, P=4.5×10−6). The expression levels of IL13 were positively correlated with IL5 in BEC (rho=0.35, P=1.9×10−4) and IL4 in BAL (rho=0.42, P=2.5×10−5), 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=7.4×10−7 and 0.04) but was not associated with asthma. 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.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
158.5
作者：
Chupp, Geoffrey L.;Lee, Chun Geun;Elias, Jack A.
通讯作者：
Elias, Jack A.
影响因子：
32.4
作者：
Lee, GR;Fields, PE;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.