4 research outputs found
Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort
<p><i>Objective</i>: 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. <i>Methods</i>: Correlation analyses of expression levels of GWAS-identified asthma genes and asthma-related biomarkers were performed in cells from human bronchial epithelial biopsy (BEC, <i>n</i> = 107) and bronchial alveolar lavage (BAL, <i>n</i> = 94). <i>Results</i>: Expression levels of asthma genes between BEC and BAL and with asthma or asthma severity were weakly correlated. The expression levels of <i>IL18R1</i> were consistently higher in asthma than controls or in severe asthma than mild/moderate asthma in BEC and BAL (<i>p</i> < 0.05). In <i>RAD50-IL13</i> region, the expression levels of <i>RAD50</i>, not <i>IL4, IL5</i>, or <i>IL13</i>, were positively correlated between BEC and BAL (ρ = 0.53, <i>P</i> = 4.5 × 10<sup>−6</sup>). The expression levels of <i>IL13</i> were positively correlated with <i>IL5</i> in BEC (ρ = 0.35, <i>P</i> = 1.9 × 10<sup>−4</sup>) and <i>IL4</i> in BAL (ρ = 0.42, <i>P</i> = 2.5 × 10<sup>−5</sup>), respectively. rs3798134 in <i>RAD50</i>, a GWAS-identified SNP, was correlated with <i>IL13</i> expression and the expression levels of <i>IL13</i> were correlated with asthma (<i>P</i> = 0.03). rs17772583 in <i>RAD50</i> was significantly correlated with <i>RAD50</i> expression in BAL and BEC (<i>P</i> = 7.4 × 10<sup>−7</sup> and 0.04) but was not associated with asthma. <i>Conclusions</i>: This is the first report studying the expression of GWAS-identified asthma genes in BEC and BAL. <i>IL13</i>, rather than <i>RAD50, IL4</i>, or <i>IL5</i>, 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.</p
Hospitalizations and Medications.
<p>All data are presented in No (%). Intensive Care Unit (ICU), Emergency Room (ER).</p
Baseline Characteristics of Study Participants.
<p>*Significant difference in Caucasian and African race among ETS and non-ETS group in Non-severe asthma. The P-value (P<0.05) is calculated by the Pearson chi-square test. High dose corticosteroid defined as twice a week inhaled corticosteroids and/or weekly systemic corticosteroids. “Unkown” does not wish to declare or does not know his/her ethnicity.</p
Analysis of total SOD activity in all asthmatics exposed to ETS or non-ETS.
<p>Asthmatic subjects exposed to ETS have significantly lower SOD activity (p = 0.04).</p