Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis
ObjectivesHTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples.MethodsWe enrolled peripheral blood samples from 235 patients with RA, 30 ost...
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Frontiers Media S.A.
2022-12-01
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| author | Jianan Zhao Jianan Zhao Jianan Zhao Lingxia Xu Lingxia Xu Lingxia Xu Cen Chang Cen Chang Cen Chang Ping Jiang Ping Jiang Ping Jiang Kai Wei Kai Wei Kai Wei Yiming Shi Yiming Shi Yiming Shi Linshuai Xu Linshuai Xu Linshuai Xu Yixin Zheng Yixin Zheng Yixin Zheng Yu Shan Yu Shan Yu Shan Yanqin Bian Yanqin Bian Yanqin Bian Li Li Li Li Li Li Shicheng Guo Shicheng Guo Steven J. Schrodi Steven J. Schrodi Rongsheng Wang Rongsheng Wang Rongsheng Wang Dongyi He Dongyi He Dongyi He Dongyi He |
| author_facet | Jianan Zhao Jianan Zhao Jianan Zhao Lingxia Xu Lingxia Xu Lingxia Xu Cen Chang Cen Chang Cen Chang Ping Jiang Ping Jiang Ping Jiang Kai Wei Kai Wei Kai Wei Yiming Shi Yiming Shi Yiming Shi Linshuai Xu Linshuai Xu Linshuai Xu Yixin Zheng Yixin Zheng Yixin Zheng Yu Shan Yu Shan Yu Shan Yanqin Bian Yanqin Bian Yanqin Bian Li Li Li Li Li Li Shicheng Guo Shicheng Guo Steven J. Schrodi Steven J. Schrodi Rongsheng Wang Rongsheng Wang Rongsheng Wang Dongyi He Dongyi He Dongyi He Dongyi He |
| author_sort | Jianan Zhao |
| collection | DOAJ |
| description | ObjectivesHTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples.MethodsWe enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about 218 bp from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around HTR2A cg15692052 from patients were analyzed by targeted methylation sequencing.ResultsWe measured methylation status for 7 CpGs in the promoter region of HTR2A and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10-5). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, P=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (FDR=0.02 and 2.81 x 10-6) is signficantly increased while TTTTTCC (FDR =0.01) and TTTTTTT(FDR =6.92 x 10-3) 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.ConclusionsIn our study, we found signficant hypermethylation of promoter region of HTR2A which indicates the potential clinical diagnostic role in rheumatoid arthritis. |
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| spelling | doaj.art-f03036ec809a4c59ba578eb00d2a35672022-12-22T04:40:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10544511054451Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritisJianan Zhao0Jianan Zhao1Jianan Zhao2Lingxia Xu3Lingxia Xu4Lingxia Xu5Cen Chang6Cen Chang7Cen Chang8Ping Jiang9Ping Jiang10Ping Jiang11Kai Wei12Kai Wei13Kai Wei14Yiming Shi15Yiming Shi16Yiming Shi17Linshuai Xu18Linshuai Xu19Linshuai Xu20Yixin Zheng21Yixin Zheng22Yixin Zheng23Yu Shan24Yu Shan25Yu Shan26Yanqin Bian27Yanqin Bian28Yanqin Bian29Li Li30Li Li31Li Li32Shicheng Guo33Shicheng Guo34Steven J. Schrodi35Steven J. Schrodi36Rongsheng Wang37Rongsheng Wang38Rongsheng Wang39Dongyi He40Dongyi He41Dongyi He42Dongyi He43Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaComputation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesComputation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaGuanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaInstitute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, ChinaArthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, ChinaObjectivesHTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples.MethodsWe enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about 218 bp from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around HTR2A cg15692052 from patients were analyzed by targeted methylation sequencing.ResultsWe measured methylation status for 7 CpGs in the promoter region of HTR2A and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10-5). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, P=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (FDR=0.02 and 2.81 x 10-6) is signficantly increased while TTTTTCC (FDR =0.01) and TTTTTTT(FDR =6.92 x 10-3) 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.ConclusionsIn our study, we found signficant hypermethylation of promoter region of HTR2A which indicates the potential clinical diagnostic role in rheumatoid arthritis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1054451/fullrheumatoid arthritiscirculating methylation levelHTR2Ainflammationdisease activity |
| spellingShingle | Jianan Zhao Jianan Zhao Jianan Zhao Lingxia Xu Lingxia Xu Lingxia Xu Cen Chang Cen Chang Cen Chang Ping Jiang Ping Jiang Ping Jiang Kai Wei Kai Wei Kai Wei Yiming Shi Yiming Shi Yiming Shi Linshuai Xu Linshuai Xu Linshuai Xu Yixin Zheng Yixin Zheng Yixin Zheng Yu Shan Yu Shan Yu Shan Yanqin Bian Yanqin Bian Yanqin Bian Li Li Li Li Li Li Shicheng Guo Shicheng Guo Steven J. Schrodi Steven J. Schrodi Rongsheng Wang Rongsheng Wang Rongsheng Wang Dongyi He Dongyi He Dongyi He Dongyi He Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis Frontiers in Immunology rheumatoid arthritis circulating methylation level HTR2A inflammation disease activity |
| title | Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis |
| title_full | Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis |
| title_fullStr | Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis |
| title_full_unstemmed | Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis |
| title_short | Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis |
| title_sort | circulating methylation level of htr2a is associated with inflammation and disease activity in rheumatoid arthritis |
| topic | rheumatoid arthritis circulating methylation level HTR2A inflammation disease activity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1054451/full |
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