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Updated: Sep 17, 2025
Targeted DNA Methylation Analysis by Next-generation Sequencing
Published on: February 24, 2015
HTR2A DNA methylation as a diagnostic biomarker for rheumatoid arthritis: a validation study using targeted
Jianan Zhao1,2,3, Binghen He4, Yunshen Li1,2,3
1Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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 and its subtypes.
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