Evidence map›Paper›PMID 24812288›Full record

ArticleAnnals of the rheumatic diseases2015

Genome-wide DNA methylation analysis in dermal fibroblasts from patients with diffuse and limited systemic sclerosis reveals common and subset-specific DNA methylation aberrancies.

Nezam Altorok, Pei-Suen Tsou, Patrick Coit, Dinesh Khanna, Amr H Sawalha

Abstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
9.3field-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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Current Concepts on the Pathogenesis of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023
    Review
  15. Article
  16. Article
  17. Fli1 and Tissue Fibrosis in Various Diseases.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022
    Review
  20. Review

20 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 3 institutions in 1 country.

Nezam AltorokDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Division of Rheumatology, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio, USA.
Pei-Suen TsouDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA.
Patrick CoitDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Dinesh KhannaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA.
Amr H SawalhaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan–Ann Arbor · USScleroderma Foundation · USUniversity of Toledo Medical Center · US

Funding

Role of DNA methylation in lupusR01AI097134 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Amr H Sawalha · 2013 to 2026
$4.5M
Outcomes Research in Rheumatic DiseasesK24AR063120 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KHANNA, DINESH · 2012 to 2022
$1.6M
NIAID NIH HHS R01 AI097134NIAID NIH HHS R01AI097134NIAMS NIH HHS K24 AR063120NIAMS NIH HHS K24 AR063120-02
6 · The paper itself

Abstract

backgroundThe aetiology of systemic sclerosis (SSc) is not clear, but there is an emerging evidence of gene-specific epigenetic dysregulation in the pathogenesis of SSc.

methodsWe performed a genome-wide DNA methylation study in dermal fibroblasts in six diffuse cutaneous SSc (dSSc) patients, six limited cutaneous SSc (lSSc) patients compared with 12 age-matched, sex-matched and ethnicity-matched healthy controls. Cytosine methylation was quantified in more than 485 000 methylation sites across the genome. Differentially methylated CpG sites between patients and controls with a fold difference ≥1.2 were identified. Quantitative real-time RT-PCR was performed to assess correlation between DNA methylation changes and gene expression levels.

resultsWe identified 2710 and 1021 differentially methylated CpG sites in dSSc and lSSc, respectively. Of the differentially methylated sites, 61% in dSSc and 90% in lSSc were hypomethylated. There were only 203 CpG sites differentially methylated in both dSSc and lSSc, representing 118 hypomethylated and 6 hypermethylated genes. Common hypomethylated genes include ITGA9, encoding an α integrin. Other relevant genes such as ADAM12, COL23A1, COL4A2 and MYO1E, and transcription factors genes RUNX1, RUNX2 and RUNX3 were also hypomethylated in both dSSc and lSSc. Pathway analysis of differentially methylated genes in both dSSc and lSSc revealed enrichment of genes involved in extracellular matrix-receptor interaction and focal adhesion. We demonstrate significant correlation between DNA methylation status and gene expression in the majority of genes evaluated.

conclusionsOur data highlight common and subset-specific aberrancies in dSSc and lSSc fibroblasts at the epigenomic levels and identify novel candidate genes in SSc.

Indexed as

DNA MethylationAdultAgedEpigenomicsFemaleFibroblastsGenome-Wide Association StudyHumansMaleMiddle AgedScleroderma, DiffuseScleroderma, LimitedSkinAutoimmunityFibroblastsSystemic Sclerosis

Identifiers

PMID24812288
PMCPMC4224992
OpenAlexW2119143823

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.