# Integrative analysis of DNA methylation and inflammatory protein biomarkers in hypertension

**Authors:** Min Zhu, Jin Zhang, Jing Ma, Xiaofeng Tang, Yan Wang, Dingliang Zhu

PMC · DOI: 10.3389/fimmu.2026.1671540 · Frontiers in Immunology · 2026-02-11

## TL;DR

This study explores how DNA methylation and inflammatory proteins are linked in hypertension patients and how they relate to organ damage.

## Contribution

The study identifies novel associations between DNA methylation and inflammatory biomarkers in hypertension.

## Key findings

- 771 significant associations were found between CpG sites and inflammatory proteins with FDR < 0.05.
- 39 pQTMs were associated with urine albumin-creatinine ratio, and 82 with carotid intima-media thickness.

## Abstract

To investigate the relationship between inflammation and hypertension by comparing epigenetic and serum biomarkers of inflammation and their association with target organ damage (TOD).

The epigenome-wide methylation profiles of peripheral leukocyte DNA from 176 patients with hypertension were analyzed using Illumina Infinium Methylation EPIC BeadChips. The commercially available Olink® Target 96 Inflammation panels were utilized to evaluate markers associated with inflammation. We identified CpG-protein association protein quantitative trait methylation loci (pQTMs) using mixed linear regression, adjusting for potential confounders. The possible roles of the discovered pQTMs were ascertained by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses. The association between pQTMs and TOD was also analyzed.

In our analysis, we found 771 significant associations across 11 biomarkers, with a false discovery rate (FDR) of less than 0.05. Lambda estimates ranged from 0.847 to 1.202. Among these, 39 pQTMs showed an association with urine albumin-creatinine ratio, while 82 pQTMs showed an association with carotid intima-media thickness.

Our findings contribute to the understanding of inflammatory biomarkers associated with alterations in DNA methylation in hypertension. However, these results will need to be validated in future studies.

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, FAT1 (FAT atypical cadherin 1) [NCBI Gene 2195] {aka CDHF7, CDHR8, FAT, ME5, hFat1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}, PTPRN2 (protein tyrosine phosphatase receptor type N2) [NCBI Gene 5799] {aka IA-2beta, IAR, ICAAR, PTPRP, R-PTP-N2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, F11 (coagulation factor XI) [NCBI Gene 2160] {aka FXI, PTA}, IL18R1 (interleukin 18 receptor 1) [NCBI Gene 8809] {aka CD218a, CDw218a, IL-18R, IL-18R-alpha, IL-18Ralpha, IL-1Rrp}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL10RA (interleukin 10 receptor subunit alpha) [NCBI Gene 3587] {aka CD210, CD210a, CDW210A, HIL-10R, IL-10R1, IL10R}, CCL7 (C-C motif chemokine ligand 7) [NCBI Gene 6354] {aka FIC, MARC, MCP-3, MCP3, NC28, SCYA6}, FGF5 (fibroblast growth factor 5) [NCBI Gene 2250] {aka HBGF-5, Smag-82, TCMGLY}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, PGAM1 (phosphoglycerate mutase 1) [NCBI Gene 5223] {aka HEL-S-35, PGAM-B, PGAMA}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CX3CL1 (C-X3-C motif chemokine ligand 1) [NCBI Gene 6376] {aka ABCD-3, C3Xkine, CXC3, CXC3C, NTN, NTT}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IGSF3 (immunoglobulin superfamily member 3) [NCBI Gene 3321] {aka EWI-3, LCDD, V8}
- **Diseases:** COPD (MESH:D029424), dementia (MESH:D003704), stroke (MESH:D020521), membranous nephropathy (MESH:D015433), type 1 and type 2 diabetes (MESH:D003924), obesity (MESH:D009765), Renal Disease (MESH:D007674), inflammatory bowel disease (MESH:D015212), heart failure (MESH:D006333), TOD (MESH:D000092124), LVMI (MESH:C536030), cognitive dysfunction (MESH:D003072), premature death (MESH:D003643), Hypertension (MESH:D006973), coronary heart disease (MESH:D003327), Inflammation (MESH:D007249), cardiometabolic diseases (MESH:D024821), rheumatoid arthritis (MESH:D001172), hemorrhagic stroke (MESH:D000083302), chronic kidney disease (MESH:D051436), cardiovascular disease (MESH:D002318), myocardial infarction (MESH:D009203), cancer (MESH:D009369), diabetes (MESH:D003920), end-stage renal disease (MESH:D007676), ischemic heart diseases (MESH:D017202)
- **Chemicals:** glucose (MESH:D005947), creatinine (MESH:D003404), sodium (MESH:D012964)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932573/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932573/full.md

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Source: https://tomesphere.com/paper/PMC12932573