当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY期刊下所有文献 > Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response.

Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response.

Abstract：

:Antenatal corticosteroids enhance lung maturation. However, the importance of glucocorticoid genes on early lung development, asthma susceptibility, and treatment response remains unknown. We investigated whether glucocorticoid genes are important during lung development and their role in asthma susceptibility and treatment response. We identified genes that were differentially expressed by corticosteroids in two of three genomic datasets: lymphoblastoid cell lines of participants in the Childhood Asthma Management Program, a glucocorticoid chromatin immunoprecipitation/RNA sequencing experiment, or a murine model; these genes made up the glucocorticoid gene set (GCGS). Using gene expression profiles from 38 human fetal lungs and C57BL/6J murine fetal lungs, we identified developmental genes that were in the top 5% of genes contributing to the top three principal components (PCs) most highly associated with post-conceptional age. Glucocorticoid genes that were enriched in this set of developmental genes were then included in the developmental glucocorticoid gene set (DGGS). We then investigated whether glucocorticoid genes are important during lung development, and their role in asthma susceptibility and treatment response. A total of 232 genes were included in the GCGS. Analysis of gene expression demonstrated that glucocorticoid genes were enriched in lung development (P = 7.02 × 10(-26)). The developmental GCGS was enriched for genes that were differentially expressed between subjects with asthma and control subjects (P = 4.26 × 10(-3)) and were enriched after treatment of subjects with asthma with inhaled corticosteroids (P < 2.72 × 10(-4)). Our results show that glucocorticoid genes are overrepresented among genes implicated in fetal lung development. These genes influence asthma susceptibility and treatment response, suggesting their involvement in the early ontogeny of asthma.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Sharma S,Kho AT,Chhabra D,Qiu W,Gaedigk R,Vyhlidal CA,Leeder JS,Barraza-Villarreal A,London SJ,Gilliland F,Raby BA,Weiss ST,Tantisira KG

doi

10.1165/rcmb.2014-0109OC

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

543-53

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

杂志文章

在线工具

Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response.