Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles

摘要: Background Children with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration lung function, significant consumption health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children given a diagnosis therapy-resistant (or therapy-refractory) (SA). Objective We sought deepen our understanding childhood SA by analyzing gene expression modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes. Methods Gene was analyzed using Cap Analysis Expression (n = 13), controlled persistent 15), age-matched healthy subjects 9). sequencing detects start sites known novel mRNAs noncoding RNAs. Results Sample groups could be separated hierarchical clustering on 1305 differentially expressed sites, including 816 genes several transcripts. Ten 13 tested transcripts were validated means RT-PCR Sanger sequencing. RAR-related orphan receptor A  (RORA) , which has been linked genome-wide association studies, significantly upregulated patients SA. network revealed decreased glucocorticoid signaling increased activity mitogen-activated protein kinase Jun cascades Conclusion Circulating leukocytes from those distinct profiles, demonstrating possible development specific molecular biomarkers supporting need for therapeutic approaches.