Evidence map›Paper›PMID 26248552›Full record

ArticleBMC medicine2015

Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy.

Elisabet Agardh, Annika Lundstig, Alexander Perfilyev, Petr Volkov, Tove Freiburghaus, Eero Lindholm, Tina Rönn, Carl-David Agardh, Charlotte Ling

Open access · goldAbstract read
In one paragraph

Article in BMC medicine, 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, 144 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Evaluating the Influence ofBiomolecules · 2025
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  11. CD44, ACAN, PLVAP, and HBEGF Emerged as Potential Biomarkers in Diabetic Retinopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Article
  12. Article
  13. Article
  14. DNA Methylation Profiles ofBiomedicines · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. International journal of ophthalmology · 2024
    Article
  19. Article
  20. Article

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

9 authors at 2 institutions in 1 country.

Elisabet AgardhDepartment of Clinical Sciences, Ophthalmology, Lund University, Scania University Hospital, 205 02, Malmö, Sweden. elisabet.agardh@med.lu.se.
Annika LundstigDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. lundstig@telia.com.
Alexander PerfilyevDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. alexander.perfilyev@med.lu.se.
Petr VolkovDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. petr.volkov@med.lu.se.
Tove FreiburghausDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. tovefreiburghaus@gmail.com.
Eero LindholmDepartment of Clinical Sciences, Endocrinology, Lund University, Scania University Hospital, 205 02, Malmö, Sweden. eero.lindholm@med.lu.se.
Tina RönnDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. tina.ronn@med.lu.se.
Carl-David AgardhDepartment of Clinical Sciences, Endocrinology, Lund University, Scania University Hospital, 205 02, Malmö, Sweden. Carl-david.agardh@med.lu.se.
Charlotte LingDepartment of Clinical Sciences, Epigenetics and Diabetes Unit, Lund University Diabetes Centre, CRC, Scania University Hospital, 205 02, Malmö, Sweden. charlotte.ling@med.lu.se.
Scania (Sweden) · SELund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpigenetic variation has been linked to several human diseases. Proliferative diabetic retinopathy (PDR) is a major cause of vision loss in subjects with diabetes. However, studies examining the association between PDR and the genome-wide DNA methylation pattern are lacking. Our aim was to identify epigenetic modifications that associate with and predict PDR in subjects with type 1 diabetes (T1D).

methodsDNA methylation was analyzed genome-wide in 485,577 sites in blood from cases with PDR (n = 28), controls (n = 30), and in a prospective cohort (n = 7). False discovery rate analysis was used to correct the data for multiple testing. Study participants with T1D diagnosed before 30 years of age and insulin treatment within 1 year from diagnosis were selected based on 1) subjects classified as having PDR (cases) and 2) subjects with T1D who had had diabetes for at least 10 years when blood DNA was sampled and classified as having no/mild diabetic retinopathy also after an 8.7-year follow-up (controls). DNA methylation was also analyzed in a prospective cohort including seven subjects with T1D who had no/mild diabetic retinopathy when blood samples were taken, but who developed PDR within 6.3 years (converters). The retinopathy level was classified by fundus photography.

resultsWe identified differential DNA methylation of 349 CpG sites representing 233 unique genes including TNF, CHI3L1 (also known as YKL-40), CHN2, GIPR, GLRA1, GPX1, AHRR, and BCOR in cases with PDR compared with controls. The majority of these sites (79 %) showed decreased DNA methylation in cases with PDR. The Natural Killer cell-mediated cytotoxicity pathway was found to be significantly (P = 0.006) enriched among differentially methylated genes in cases with PDR. We also identified differential DNA methylation of 28 CpG sites representing 17 genes (e.g. AHRR, GIPR, GLRA1, and BCOR) with P <0.05 in the prospective cohort, which is more than expected by chance (P = 0.0096).

conclusionsSubjects with T1D and PDR exhibit altered DNA methylation patterns in blood. Some of these epigenetic changes may predict the development of PDR, suggesting that DNA methylation may be used as a prospective marker of PDR.

Indexed as

AdultCohort StudiesDiabetes Mellitus, Type 1Diabetic RetinopathyDNA MethylationEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedProspective Studies

Identifiers

PMID26248552
PMCPMC4527111
OpenAlexW1874574653

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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.