DNA甲基化作为类风湿性关节炎的诊断生物标志物：一项使用靶向测序的验证研究

DNA methylation as a diagnostic biomarker for rheumatoid arthritis: a validation study using targeted sequencing.

作者信息

Zhao Jianan, He Binghen, Li Yunshen, Shan Yu, Wei Kai, Jiang Ping, Shi Yiming, Zheng Yixin, Zhao Fuyu, Yang Guizhen, Li Qianqian, Zhou Mi, Guo Shicheng, Zheng Yuejuan, Jiao Juan, Wang Rongsheng, Chang Cen, Lv Liangjing

机构信息

Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Epigenomics. 2025 Jun 27:1-11. doi: 10.1080/17501911.2025.2523231.

DOI:10.1080/17501911.2025.2523231

PMID:40576051

Abstract

OBJECTIVES

To validate the potential of the serotonin receptor encoded by 5-hydroxytryptamine receptor 2A (HTR2A) cg15692052 DNA methylation as a diagnostic biomarker for rheumatoid arthritis (RA) and its subtypes.

METHODS

MethylTarget targeted region methylation sequencing technology was employed to analyze the DNA methylation levels of HTR2A cg15692052 in RA, health control, ankylosing spondylitis, psoriatic arthritis, gout, systemic lupus erythematosus, dermatomyositis, and primary Sjögren's syndrome patients within the region of chr13:46898190~chr13:46897976. Machine learning algorithms were used to analyze data.

RESULTS

Compared to the HC group, RA patients and four serological subtypes of RA (RF-negative RA, RF/CCP double-positive, RF/CCP double-negative, and CCP-negative RA) exhibited significantly higher levels of cg15692052 methylation ( < 0.05). Methylation levels in RA patients and its four serological subtypes were significantly positively correlated with erythrocyte sedimentation rate or C-reactive protein ( < 0.05). cg15692052 methylation levels combined with different clinical features can significantly distinguish RA patients with AUCs ranging from 0.672 to 0.757, RF/CCP double-negative patients with AUCs from 0.825 to 0.966, RF/CCP double-positive RA patients with AUCs from 0.714 to 0.846, and RF-negative RA patients with AUCs from 0.928 to 0.932.

CONCLUSIONS

The cg15692052 DNA methylation level can serve as a diagnostic biomarker for RA and its subtypes.

摘要

目的

验证由5-羟色胺受体2A（HTR2A）基因座cg15692052的DNA甲基化所编码的血清素受体作为类风湿关节炎（RA）及其亚型诊断生物标志物的潜力。

方法

采用甲基化靶向区域甲基化测序技术，分析13号染色体：46898190~13号染色体：46897976区域内RA患者、健康对照、强直性脊柱炎、银屑病关节炎、痛风、系统性红斑狼疮、皮肌炎和原发性干燥综合征患者的HTR2A基因座cg15692052的DNA甲基化水平。使用机器学习算法分析数据。

结果

与健康对照（HC）组相比，RA患者及RA的四种血清学亚型（RF阴性RA、RF/CCP双阳性、RF/CCP双阴性和CCP阴性RA）的cg15692052甲基化水平显著更高（<0.05）。RA患者及其四种血清学亚型的甲基化水平与红细胞沉降率或C反应蛋白显著正相关（<0.05）。结合不同临床特征的cg15692052甲基化水平能够显著区分RA患者（曲线下面积[AUC]范围为0.672至0.757）、RF/CCP双阴性患者（AUC范围为0.825至0.966）、RF/CCP双阳性RA患者（AUC范围为0.714至0.846）以及RF阴性RA患者（AUC范围为0.928至0.932）。