Hypomethylation of the low-density lipoprotein receptor class A domain containing 4 gene in rheumatoid arthritis

Jingjing Song; Zhen Liu; Fan Yang; Ting Zhang; Zhenglun Pan

doi:10.1016/j.clim.2025.110441

Hypomethylation of the low-density lipoprotein receptor class A domain containing 4 gene in rheumatoid arthritis

Clin Immunol. 2025 Jan 25:110441. doi: 10.1016/j.clim.2025.110441. Online ahead of print.

Authors

Jingjing Song¹, Zhen Liu¹, Fan Yang¹, Ting Zhang¹, Zhenglun Pan²

Affiliations

¹ Department of Rheumatology, Qilu Hospital of Shandong University(Qingdao), Qingdao, China.
² Department of Rheumatology, Qilu Hospital of Shandong University(Qingdao), Qingdao, China. Electronic address: panzhenglun@126.com.

PMID: 39870147
DOI: 10.1016/j.clim.2025.110441

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease linked to epigenetic changes, particularly DNA methylation. While LDLRAD4 has been implicated in RA through GWAS, its role in RA via methylation remains unclear.

Objectives: To investigate LDLRAD4 methylation patterns in RA and evaluate its potential as a diagnostic and inflammatory biomarker.

Methods: We assessed DNA methylation at specific CpG sites within LDLRAD4 in 150 RA patients and 150 healthy controls. Clinical data, including disease duration and inflammatory markers, were collected.

Results: RA patients showed significant hypomethylation of LDLRAD4, especially in the LDLRAD4-43 and LDLRAD4-44 regions. ROC analysis yielded an AUC of 0.841, indicating strong diagnostic potential. Methylation levels correlated negatively with ESR, CRP and DAS28 in the RF+/CCP- subgroup.

Conclusions: LDLRAD4 DNA present hypomethylation in rheumatoid arthritis, and methylation levels are correlated with inflammatory indicator, possibly via TGF-β signaling. Further research is needed to explore its therapeutic potential.

Keywords: DNA methylation; Epigenetics; Methyl target approach; Rheumatoid arthritis.