Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome. To iden...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2014-12, Vol.190 (11), p.1263-1272
Main Authors: Yang, Ivana V, Pedersen, Brent S, Rabinovich, Einat, Hennessy, Corinne E, Davidson, Elizabeth J, Murphy, Elissa, Guardela, Brenda Juan, Tedrow, John R, Zhang, Yingze, Singh, Mandal K, Correll, Mick, Schwarz, Marvin I, Geraci, Mark, Sciurba, Frank C, Quackenbush, John, Spira, Avrum, Kaminski, Naftali, Schwartz, David A
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - therapeutic use
Arrays
Cancer
Case-Control Studies
Consortia
Data analysis
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic - physiology
Epigenetics
Female
Gene Expression
Genetic Markers
Genomes
Humans
Idiopathic Pulmonary Fibrosis - genetics
Immunosuppressive Agents - therapeutic use
Lung diseases
Male
Middle Aged
Original
Pathogenesis
Pulmonary fibrosis
Quality control
Quantitative Trait Loci - genetics
Smoking - epidemiology
Smooth muscle
Transcriptome - genetics
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Summary:Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome. To identify methylation marks that modify gene expression in IPF lung. We assessed DNA methylation (comprehensive high-throughput arrays for relative methylation arrays [CHARM]) and gene expression (Agilent gene expression arrays) in 94 patients with IPF and 67 control subjects, and performed integrative genomic analyses to define methylation-gene expression relationships in IPF lung. We validated methylation changes by a targeted analysis (Epityper), and performed functional validation of one of the genes identified by our analysis. We identified 2,130 differentially methylated regions (DMRs;
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201408-1452oc