HTR2A DNA methylation as a diagnostic biomarker for rheumatoid arthritis: a validation study using targeted sequencing

作者：Jianan Zhao, B. He, Yunshen Li, Yu Shan, Kai Wei, Ping Jiang, Yiming Shi, Yixin Zheng, Fuyu Zhao, Gui‐Zhen Yang, Qianqian Li, Mi Zhou, Shicheng Guo, Yuejuan Zheng, Juan Jiao, Rongsheng Wang, Cen Chang, Liangjing Lv · 发表于：Epigenomics · 年份：2025 · DOI：10.1080/17501911.2025.2523231 · 被引用次数：5 · 研究领域：Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments、Systemic Sclerosis and Related Diseases

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 MethylTargetTM 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 HTR2A cg15692052 methylation (p < 0.05). Methylation levels in RA patients and its four serological subtypes were significantly positively correlated with erythrocyte sedimentation rate or C-reactive protein (p < 0.05). HTR2A 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 HTR2A cg15692052 DNA methylation level can serve as a diagnostic biomarker for RA an...