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Respir Res. 2020 Jan 28;21(1):31. doi: 10.1186/s12931-020-1295-4.

Expression of SMARCD1 interacts with age in association with asthma control on inhaled corticosteroid therapy.

Author information

1
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
2
PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, 401 Park Drive, Suite 401, Boston, MA, 02215-5301, USA.
3
Program in Molecular and Integrative Physiological Sciences, Departments of Environmental Health and Genetics & Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
4
Center for Genes, Environment and Health, Department of Pediatrics, National Jewish Health, Denver, CO, USA.
5
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
6
Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
7
Division of Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, MA, USA.
8
Centro de Neumologia Pediatrica, San Juan, PR, USA.
9
PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, 401 Park Drive, Suite 401, Boston, MA, 02215-5301, USA. ann.wu@childrens.harvard.edu.

Abstract

BACKGROUND:

Global gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context.

METHODS:

We used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments & Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age.

RESULTS:

The SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10- 9), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10- 8). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells.

CONCLUSION:

Focusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids.

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