Genome-Wide DNA Methylation Patterns In Interstitial Lung Disease (ILD) And Chronic Obstructive Lung Disease (COPD)

Yang, Ivana V.; Pedersen, Brent S.; Hennessy, Corinne E.; Davidson, Elizabeth; Bonney, Megan; Leach, Sonia M.; Brown, Joseph A.; Turner, Julia; Guardela, Brenda Juan; Tedrow, John; Correll, Mick; Geraci, Mark W.; Kaminski, Naftali; Quackenbush, John; Sciurba, Frank C.; Spira, Avrum; Schwartz, David

doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2667

Cited by 3 publications

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“…We and others have reported differential methylation of the GATA-4 gene in both sputum and lung tissue from patients with COPD, as compared to controls (Sood et al, 2010;Yang et al, 2011). The present study takes those findings one step further to identify a link between GATA-4 gene methylation in sputum DNA and self-reported health status among subjects with COPD.…”

Section: Discussionmentioning

confidence: 67%

Epigenetic Change (GATA-4 Gene Methylation) Is Associated With Health Status in Chronic Obstructive Pulmonary Disease

Meek

Sood

Petersen

et al. 2014

Biological Research For Nursing

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Gene methylation is an epigenetic change that involves a heritable modification of chromatin structure that alters gene expression without a change in DNA sequence. It has previously been shown that methylation of the GATA-4 gene promoter region in sputum DNA is associated with low lung function and increased odds of chronic obstructive pulmonary disease (COPD) among smokers. Given these findings, we hypothesized that GATA-4 gene methylation in sputum DNA would be associated with low health status, as measured by the St. George's Respiratory Questionnaire (SGRQ), in subjects with COPD. Self-reported SGRQ, spirometry, and induced sputum samples were obtained from 168 COPD subjects from the Lovelace Smokers Cohort. GATA-4 gene methylation was evaluated in sputum DNA using nested methylation-specific polymerase chain reaction (PCR) assays. Using general linear model with Poisson regression, we found that GATA-4 gene methylation was significantly associated with overall lower SGRQ health status (parameter estimate = .296, p < .001). This finding remained significant even after controlling for age, lung function, and other covariates. In an additional analysis using logistic regression and comparing extreme tertiles of overall SGRQ score, we confirmed that GATA-4 gene methylation was associated with a 3-fold increase in risk of poor health status (OR 2.95 and p = .028). The unexplored links between epigenetic changes and psychosocial factors such as health status are critical gaps in the literature. This study is the first to suggest that airway GATA-4 gene methylation status may independently predict health status in individuals with COPD.

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Section: Discussionmentioning

confidence: 67%

Epigenetic Change (GATA-4 Gene Methylation) Is Associated With Health Status in Chronic Obstructive Pulmonary Disease

Meek

Sood

Petersen

et al. 2014

Biological Research For Nursing

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“…The Lung Genomics Research Consortium (LGRC; lung-genomics.org) has profiled lung tissue DNA from 100 individuals with IPF and 79 controls on Comprehensive High-Throughput Arrays for Relative Methylation (CHARM) [112, 113]. Our results revealed that the majority of the 2130 differentially methylated regions (DMRs) are located within CpG island ‘shores’, areas of lower CpG density near CpG islands and are contained within genes [114]. Our analysis demonstrates more extensive overlap in methylation and expression and a statistically significant enrichment for inverse relationships of methylation and expression.…”

Section: Epigenetic Studies In Ipfmentioning

confidence: 99%

Epigenetics of idiopathic pulmonary fibrosis

Yang

Schwartz

2015

Translational Research

Self Cite

122

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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Recent work by our and other groups has identified strong genetic predisposition factors for the development of pulmonary fibrosis while cigarette smoke remains the most strongly associated environmental exposure risk factor. Gene expression profiling studies of IPF lung have taught us quite a bit about the biology of this fatal disease and those in peripheral blood have provided important biomarkers. However, epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptional changes associated with disease development. Moreover, epigenetic marks represent a promising therapeutic target for IPF. In this review, we will introduce the disease, summarize genetic and gene expression studies in IPF, discuss exposures relevant to IPF and known epigenetic changes associated with cigarette smoke exposure, and summarize epigenetic studies conducted so far in IPF. We will end by discussing limitations, challenges and future opportunities in this field.

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“…The Lung Genomics Research Consortium (LGRC [101]) has profiled lung tissue DNA from 100 individuals with IPF and 79 controls using Comprehensive High-Throughput Arrays for Relative Methylation (CHARM) [73,74]. Our results revealed that the majority of differentially methylated regions are hypomethylated in disease, located within CpG island ‘shores’ (areas of lower CpG density near CpG islands) and contained within genes [75]. These findings are different from studies in the lung cancer field that have focused on CpG islands in promoter regions of genes as main methylation sites that control gene expression; we are in the process of correlating genome-wide DNA methylation patterns with global changes in gene expression in IPF lungs.…”

Section: Epigenetic Studies In Ipfmentioning

confidence: 99%

Epigenomics of Idiopathic Pulmonary Fibrosis

Yang

2012

Epigenomics

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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges and future directions in this field.

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Genome-Wide DNA Methylation Patterns In Interstitial Lung Disease (ILD) And Chronic Obstructive Lung Disease (COPD)

Cited by 3 publications

References 0 publications

Epigenetic Change (GATA-4 Gene Methylation) Is Associated With Health Status in Chronic Obstructive Pulmonary Disease

Epigenetic Change (GATA-4 Gene Methylation) Is Associated With Health Status in Chronic Obstructive Pulmonary Disease

Epigenetics of idiopathic pulmonary fibrosis

Epigenomics of Idiopathic Pulmonary Fibrosis

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