Evidence map›Paper›PMID 39602044›Full record

ArticleClinical rheumatology2025

HIPK3 hypomethylation as a potential epigenetic biomarker in rheumatic immune diseases with emphasis on rheumatoid arthritis.

Ping Jiang, Yi Shen, Cen Chang, Yiming Shi, Kai Wei, Jianan Zhao, Yu Shan, Yixin Zheng, Fuyu Zhao, Shicheng Guo and 1 more

Abstract read
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Article in Clinical rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Rheumatoid Arthritis: Biomarkers and the Latest Breakthroughs.International journal of molecular sciences · 2025
    Review
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

11 authors.

Ping Jiang *Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yi Shen *Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Cen Chang *Department of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yiming ShiDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Kai WeiDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Jianan ZhaoDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yu ShanDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yixin ZhengDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Fuyu ZhaoDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shicheng GuoDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Dongyi HeDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. dongyihe@medmail.com.cn.ORCID http://orcid.org/0000-0002-9948-6332

Funding

National Natural Science Funds of China 82073901National Natural Science Funds of China 82074234Research and development of traditional therapies and preparations for arthropathy and transformation of doctoral innovative talent base RCJD2021B04Shanghai Municipal Health Commission 202340274Sponsored by Shanghai Sailing Program 23YF1436300
6 · The paper itself

Abstract

objectivesThis study aimed to explore the potential of HIPK3 DNA methylation as a biomarker for rheumatoid arthritis (RA) by examining its methylation levels in various rheumatic immune diseases and analyzing its correlation with clinical indicators.

methodsWe recruited 368 participants, including patients with RA, ankylosing spondylitis (AS), GOUT, psoriatic arthritis (PSA), sjogren's syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and healthy controls (HC), and MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). We analyzed the HIPK3 methylation levels and correlated them with common clinical indicators. Transcriptome data from the GEO dataset (GSE93272) were also analyzed to assess HIPK3 mRNA expression levels in RA patients. Statistical analyses included Spearman correlation, One-Way ANOVA, Kruskal-Wallis tests, and ROC curve analysis.

resultsHIPK3 methylation levels were significantly lower in the RA, SLE, and DM groups compared to the HC group (P < 0.05). RA subgroups based on RF and CCP statuses also showed lower HIPK3 methylation levels compared to the HC group (P < 0.05). Analysis of the GEO dataset revealed significantly elevated HIPK3 mRNA expression in RA patients (P < 0.05). A negative correlation was found between HIPK3 methylation levels and ESR (r = -0.14, P = 7.1e-3), CRP (r = -0.25, P = 4.1e-7), RF (r = -0.18, P = 5.2e-4), and DAS28-CRP (r = -0.12, P = 0.04) in the RA group. ROC analysis indicated that HIPK3 methylation levels had high diagnostic value for RA (AUC = 0.742), SLE (AUC = 0.701), and DM (AUC = 0.948), especially in distinguishing seronegative RA (AUC = 0.612, 0.747, 0.836) and differentiating RA from AS (AUC = 0.788).

conclusionsThe study suggests that HIPK3 hypomethylation in peripheral blood is associated with RA and correlated with inflammatory markers, such as CRP. HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends, showing particular promise in differentiating RA from other types of arthritis. Key Points • MethylTargetTM targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HIPK3 (cg15692052). • HIPK3 methylation levels have potential as a novel biomarker for RA diagnosis and predicting inflammation trends.

Indexed as

Arthritis, RheumatoidCarrier ProteinsDNA MethylationEpigenesis, GeneticProtein Serine-Threonine KinasesRheumatic DiseasesAdultBiomarkersCase-Control StudiesFemaleHumansIntracellular Signaling Peptides and ProteinsMaleMiddle AgedROC CurveBiomarkersCarrier ProteinsHIPK3 protein, humanIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesBiomarkerDNA methylationHomeodomain-interacting protein kinase 3InflammationRheumatoid arthritis

Identifiers

PMID39602044

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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.