Dataset Information

Global methylation patterns in idiopathic pulmonary fibrosis.

ABSTRACT: BACKGROUND:Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile. METHODOLOGY/PRINCIPAL FINDINGS:Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs was hybridized to Agilent human CpG Islands Microarrays and data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages. Array results were validated using the EpiTYPER MassARRAY platform for 3 CpG islands. 625 CpG islands were differentially methylated between IPF and control lungs with an estimated False Discovery Rate less than 5%. The genes associated with the differentially methylated CpG islands are involved in regulation of apoptosis, morphogenesis and cellular biosynthetic processes. The expression of three genes (STK17B, STK3 and HIST1H2AH) with hypomethylated promoters was increased in IPF lungs. Comparison of IPF methylation patterns to lung cancer or control samples, revealed that IPF lungs display an intermediate methylation profile, partly similar to lung cancer and partly similar to control with 402 differentially methylated CpG islands overlapping between IPF and cancer. Despite their similarity to cancer, IPF lungs did not exhibit hypomethylation of long interspersed nuclear element 1 (LINE-1) retrotransposon while lung cancer samples did, suggesting that the global hypomethylation observed in cancer was not typical of IPF. CONCLUSIONS/SIGNIFICANCE:Our results provide evidence that epigenetic changes in IPF are widespread and potentially important. The partial similarity to cancer may signify similar pathogenetic mechanisms while the differences constitute IPF or cancer specific changes. Elucidating the role of these specific changes will potentially allow better understanding of the pathogenesis of IPF.

SUBMITTER: Rabinovich EI

PROVIDER: S-EPMC3323629 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Global methylation patterns in idiopathic pulmonary fibrosis.

Rabinovich Einat I EI Kapetanaki Maria G MG Steinfeld Israel I Gibson Kevin F KF Pandit Kusum V KV Yu Guoying G Yakhini Zohar Z Kaminski Naftali N

PloS one 20120410 4

<h4>Background</h4>Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile.<h4>Methodology/principal findings</h4>Immunoprecipitated methylated DNA fr ...[more]

PMID: 22506007

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Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive debilitating lung disease with considerable morbidity. Heterogeneity in epidemiologic studies means the full impact of the disease is unclear.MethodsA targeted literature search for population-based, observational studies reporting incidence and/or prevalence of IPF from January 2009 to April 2020 was conducted. Identified studies were aggregated by country. For countries with multiple publications, a weighted average was determined. Incidence and prevalence data were adjusted for between-study differences where possible. The final model included adjusted estimates of incidence and prevalence per 10,000 of the population with 95% confidence intervals. As prevalence estimates vary depending on the definitions used, estimates were based on a specific case definition of IPF.ResultsOverall, 22 studies covering 12 countries met the inclusion criteria, with 15 reporting incidence and 18 reporting prevalence estimates. The adjusted incidence estimates (per 10,000 of the population) ranged from 0.35 to 1.30 in Asia-Pacific countries, 0.09 to 0.49 in Europe, and 0.75 to 0.93 in North America. Unadjusted and adjusted incidence estimates were consistent. The adjusted prevalence estimates ranged from 0.57 to 4.51 in Asia-Pacific countries, 0.33 to 2.51 in Europe, and 2.40 to 2.98 in North America. South Korea had the highest incidence and prevalence estimates. When prevalence estimates were compared to country-specific rare disease thresholds, IPF met the definition of a rare disease in all countries except South Korea. There were notable geographic gaps for IPF epidemiologic data.ConclusionsDue to differences in study methodologies, there is worldwide variability in the reported incidence and prevalence of IPF. Based on the countries included in our analysis, we estimated the adjusted incidence and prevalence of IPF to be in the range of 0.09-1.30 and 0.33-4.51 per 10,000 persons, respectively. According to these prevalence estimates, IPF remains a rare disease. For consistency, future epidemiologic studies of IPF should take age, sex, smoking status, and the specificity of case definitions into consideration.

Dataset Information

Global methylation patterns in idiopathic pulmonary fibrosis.

Publications

Global methylation patterns in idiopathic pulmonary fibrosis.

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