AUTHOR=Zhao Jianan , Xu Lingxia , Chang Cen , Jiang Ping , Wei Kai , Shi Yiming , Xu Linshuai , Zheng Yixin , Shan Yu , Bian Yanqin , Li Li , Guo Shicheng , Schrodi Steven J. , Wang Rongsheng , He Dongyi 

TITLE=Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1054451

DOI=10.3389/fimmu.2022.1054451

ISSN=1664-3224

ABSTRACT=<sec><title>Objectives</title><p><italic>HTR2A</italic> is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of <italic>HTR2A</italic> with RA within peripheral blood samples.</p></sec><sec><title>Methods</title><p>We enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about <italic>218 bp</italic> from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around <italic>HTR2A</italic> cg15692052 from patients were analyzed by targeted methylation sequencing.</p></sec><sec><title>Results</title><p>We measured methylation status for 7 CpGs in the promoter region of <italic>HTR2A</italic> and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10<sup>-5</sup>). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, <italic>P</italic>=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (<italic>FDR</italic>=0.02 and 2.81 x 10<sup>-6</sup>) is signficantly increased while TTTTTCC (<italic>FDR</italic> =0.01) and TTTTTTT(<italic>FDR</italic> =6.92 x 10<sup>-3</sup>) are significantly decreased in RA. We find methylation haplotypes combining with RF and CCP could signficantly enhance the performance of the diagnosing RA and its comorbidities (hypertension, interstitial lung disease, and osteoporosis), especially in interstitial lung disease.</p></sec><sec><title>Conclusions</title><p>In our study, we found signficant hypermethylation of promoter region of <italic>HTR2A</italic> which indicates the potential clinical diagnostic role in rheumatoid arthritis.</p></sec>