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JCI Insight. 2016 Dec 8;1(20):e90151.

DNA methylation in lung cells is associated with asthma endotypes and genetic risk.

Author information

1
Department of Human Genetics.
2
Department of Medicine, and.
3
Department of Human Genetics,; Department of Medicine, and; Department of Statistics, University of Chicago, Chicago, Illinois, USA.
4
Department of Human Genetics,; Department of Medicine, and.

Abstract

The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctor's diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.

PMID:
27942592
PMCID:
PMC5139904
DOI:
10.1172/jci.insight.90151
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

J. Solway has been a scientific advisor for and has a financial interest in PulmOne Advanced Medical Devices Ltd., Israel, and received reimbursement for expenses. He served on the Respiratory Therapy Clinical Advisory Board for Hollister Inc., and for this received honoraria and was reimbursed for travel and meal expenses incurred during meetings. He has received a research grant from AstraZeneca Inc., from 2006 to 2014, that was administered through the University of Chicago. He has multiple patents concerning a smooth muscle gene promoter and one pending concerning a method to determine respiratory physiological parameters (6090618; 6114311; 6284743; 6291211; 6297221; 6331527; 7169764). He has consulted for Novartis Institute for Biomedical Research, for which he received an honorarium and travel reimbursement. He was a member of the scientific advisory board for Cytokinetics Inc., for which he received honoraria and travel reimbursement.

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