Song Jingjing, Liu Zhen, Yang Fan, Zhang Ting, Pan Zhenglun
Department of Rheumatology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.
Department of Rheumatology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.
Clin Immunol. 2025 Mar;272:110441. doi: 10.1016/j.clim.2025.110441. Epub 2025 Jan 25.
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.
To investigate LDLRAD4 methylation patterns in RA and evaluate its potential as a diagnostic and inflammatory biomarker.
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.
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.
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.
类风湿性关节炎（RA）是一种与表观遗传变化，特别是DNA甲基化相关的慢性炎症性疾病。虽然低密度脂蛋白受体衔接蛋白4（LDLRAD4）已通过全基因组关联研究（GWAS）与类风湿性关节炎相关联，但其通过甲基化在类风湿性关节炎中的作用仍不清楚。
研究类风湿性关节炎中LDLRAD4的甲基化模式，并评估其作为诊断和炎症生物标志物的潜力。
我们评估了150例类风湿性关节炎患者和150例健康对照者LDLRAD4内特定CpG位点的DNA甲基化情况。收集了包括病程和炎症标志物在内的临床数据。
类风湿性关节炎患者显示LDLRAD4存在显著低甲基化，尤其是在LDLRAD4-43和LDLRAD4-44区域。ROC分析得出曲线下面积（AUC）为0.841，表明其具有很强的诊断潜力。在RF+/CCP-亚组中，甲基化水平与红细胞沉降率（ESR）、C反应蛋白（CRP）和疾病活动评分28（DAS28）呈负相关。
类风湿性关节炎中LDLRAD4 DNA存在低甲基化，且甲基化水平与炎症指标相关，可能通过转化生长因子-β（TGF-β）信号通路。需要进一步研究以探索其治疗潜力。
