Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control.
Am J Respir Crit Care Med
; 195(2): 179-188, 2017 01 15.
Article
em En
| MEDLINE
| ID: mdl-27494826
ABSTRACT
RATIONALE Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches. OBJECTIVES:
To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.METHODS:
We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD4+ T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts a second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute). MEASUREMENTS AND MAINRESULTS:
In the WB discovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, <5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, <25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide.CONCLUSIONS:
Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Perfilação da Expressão Gênica
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2017
Tipo de documento:
Article