Evidence map›Paper›PMID 22736089›Full record

ArticleAnnals of the rheumatic diseases2013

DNA methylome signature in rheumatoid arthritis.

Kazuhisa Nakano, John W Whitaker, David L Boyle, Wei Wang, Gary S Firestein

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 188 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
188citing papers in PubMed, 1 pooled it
15.3field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

188 citing papers in PubMed, 1 synthesis or guideline pooled it, 349 citations in OpenAlex.

  1. Pooled it
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  9. [Neutrophil-derived Microvesicles Regulate DNA Methylation of theSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
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  11. Frontiers in medicine · 2026
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128 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kazuhisa NakanoDepartment of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
John W Whitaker
David L Boyle
Wei Wang
Gary S Firestein
University of California, San Diego · US

Funding

San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
SAN DIEGO CLINICAL AND TRANSLATIONAL RESEARCH INSTITUTEUL1RR031980 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2010 to 2011
$14.0M
NCATS NIH HHS UL1 TR000100NCRR NIH HHS UL1 RR031980NCRR NIH HHS UL1RR031980
6 · The paper itself

Abstract

objectivesEpigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed.

methodsGenomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini-Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes.

resultsRA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern.

conclusionsDifferentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis.

Indexed as

Gene Expression RegulationTranscriptomeAgedArthritis, RheumatoidCluster AnalysisDNA MethylationFemaleFibroblastsGenome-Wide Association StudyHumansMiddle AgedOligonucleotide Array Sequence AnalysisPolymerase Chain ReactionSynovial Membrane

Identifiers

PMID22736089
PMCPMC3549371
OpenAlexW2119443108

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.