Evidence map›Paper›PMID 22700861›Full record

ArticleAmerican journal of respiratory and critical care medicine2012

Altered DNA methylation profile in idiopathic pulmonary fibrosis.

Yan Y Sanders, Namasivayam Ambalavanan, Brian Halloran, Xiangyu Zhang, Hui Liu, David K Crossman, Molly Bray, Kui Zhang, Victor J Thannickal, James S Hagood

Registry-linked trialAbstract readComparative Study
In one paragraph

Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02691611 (Defining Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency), which is not on this map. Cited by 145 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02691611 completednot on this mapstarted 2015, after this paper: background citation

Defining Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency

TypeobservationalSponsorNational Jewish HealthRan2015 to 2020Enrolled39ConditionsAlpha 1-Antitrypsin Deficiency
3 · Its place in the literature

Who cites it

145 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  7. Article
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  11. Epigenome-Wide Analysis Identifies Pollution-Sensitive Loci in Fibrotic Interstitial Lung Disease.American journal of respiratory and critical care medicine · 2025
    Article
  12. From Smog to Scar: Epigenetic Signatures of Air Pollution in Interstitial Lung Disease.American journal of respiratory and critical care medicine · 2025
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  19. Review
  20. Review

85 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Yan Y SandersDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, 901 19th Street South, BMRII Room 408, Birmingham, AL 35294, USA. yans@uab.edu
Namasivayam Ambalavanan
Brian Halloran
Xiangyu Zhang
Hui Liu
David K Crossman
Molly Bray
Kui Zhang
Victor J Thannickal
James S Hagood
Pulmonary and Allergy Associates · USCenter for Genomic Science · ITPediatrics and Genetics · USUniversity of Alabama at Birmingham · USUniversity of California San Diego · US

Funding

Regulation of Fibroblast Phenotype in Lung FibrosisR01HL082818 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAGOOD, JAMES S. · 2007 to 2017
$3.7M
Oxidants and TGF-beta in Myofibroblast Differentiation/SurvivalR01HL067967 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THANNICKAL, VICTOR J. · 2001 to 2011
$2.7M
TRANSFORMING GROWTH FACTOR - BETA MEDIATES EFFECTS OF HYPOXIA IN NEWBORN LUNGR01HL092906 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMBALAVANAN, NAMASIVAYAM · 2008 to 2012
$1.9M
Epigenetic Alterations in IPF Fibroblastic FociR03HL097006 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SANDERS, YAN · 2009 to 2010
$146k
NHLBI NIH HHS R01 HL067967NHLBI NIH HHS R01HL067967NHLBI NIH HHS R01 HL082818NHLBI NIH HHS R01HL082818NHLBI NIH HHS R01 HL092906NHLBI NIH HHS R01HL092906NHLBI NIH HHS R03 HL097006NHLBI NIH HHS R03HL097006PHS HHS AHA09SDG2260095
6 · The paper itself

Abstract

rationaleDNA methylation is an important epigenetic mechanism, which often occurs in response to environmental stimuli and is crucial in regulating gene expression. It is likely that epigenetic alterations contribute to pathogenesis in idiopathic pulmonary fibrosis (IPF).

objectivesTo determine the DNA methylation changes in IPF and their effects on gene expression.

methodsTotal DNA methylation and DNA methyltransferase expression were compared in IPF and normal control lung tissues. IPF and normal tissues were subjected to comparative analysis of genome-wide DNA methylation and RNA expression using DNA hybridization to the Illumina HumanMethylation27 BeadChip and RNA hybridization to Illumina HumanHT-12 BeadChip. Functional analyses of differentially expressed and differentially methylated genes were done. Selected genes were validated at DNA, RNA, and protein levels. MEASUREMENTS AND MAIN

resultsDNA methylation status was altered in IPF. IPF samples demonstrated higher DNA methyltransferase expression without observed alterations in global DNA methylation. Genome-wide differences in DNA methylation status and RNA expression were demonstrated by array hybridization. Among the genes whose DNA methylation status and RNA expression were both significantly altered, 16 genes were hypermethylated in DNA associated with decreased mRNA expression or vice versa. We validated CLDN5, ZNF467, TP53INP1, and DDAH1 genes at the level of DNA methylation status, RNA, and protein-level expression.

conclusionsChanges in DNA methylation correspond to altered mRNA expression of a number of genes, some with known and others with previously uncharacterized roles in IPF, suggesting that DNA methylation is important in the pathogenesis of IPF.

Indexed as

AmidohydrolasesBiopsy, NeedleBlotting, WesternClaudin-5DNA MethylationDNA Modification MethylasesDown-RegulationGene Expression ProfilingGene Expression RegulationHumansIdiopathic Pulmonary FibrosisImmunohistochemistryReal-Time Polymerase Chain ReactionRNA, MessengerSampling StudiesSensitivity and SpecificityAmidohydrolasesClaudin-5CLDN5 protein, humandimethylargininaseDNA Modification MethylasesRNA, Messenger

Identifiers

PMID22700861
PMCPMC3480526
OpenAlexW2159893642

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.