{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:23:12Z","timestamp":1783102992612,"version":"3.54.6"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,11,2]]},"abstract":"\n Background<\/jats:title>\n \n Blood\u2010based DNA methylation patterns are linked to types of diseases. FKBP prolyl isomerase 5 (FKBP5), a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte\n FKBP5<\/jats:italic>\n DNA methylation in patients with dilated cardiomyopathy (DCM) remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n The present study enrolled patients with DCM (n=31) and age\u2010matched and sex\u2010matched control participants (n=43). We assessed\n FKBP5<\/jats:italic>\n CpG (cytosine\u2010phosphate\u2010guanine) methylation of CpG islands at the 5\u2032 side as well as putative promoter regions by methylation\u2010specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood.\n FKBP5<\/jats:italic>\n CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in patients with DCM. Leukocyte\n FKBP5<\/jats:italic>\n and\n IL\u20101\u03b2<\/jats:italic>\n (interleukin 1\u03b2) mRNA expression levels were significantly higher in patients with DCM than in controls. The protein expressions of DNMT1 (DNA methyltransferase 1) and DNMT3A (DNA methyltransferase 3A) in leukocytes were significantly reduced in patients with DCM. In vitro methylation assay revealed that\n FKBP5<\/jats:italic>\n promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting that the decreased\n FKBP5<\/jats:italic>\n CpG methylation was functionally associated with elevation of\n FKBP5<\/jats:italic>\n mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5\u2010expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings demonstrate a link between specific CpG hypomethylation of leukocyte\n FKBP5<\/jats:italic>\n and DCM. Blood\u2010based epigenetic modification in\n FKBP5<\/jats:italic>\n may be a novel molecular mechanism that contributes to the pathogenesis of DCM.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.121.021101","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T09:05:52Z","timestamp":1635498352000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Blood\u2010Based Epigenetic Markers of\n FKBP5<\/i>\n Gene Methylation in Patients With Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"10","author":[{"given":"Kento","family":"Wada","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-9334","authenticated-orcid":false,"given":"Tomofumi","family":"Misaka","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-3274","authenticated-orcid":false,"given":"Tetsuro","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kimishima","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-9538","authenticated-orcid":false,"given":"Takashi","family":"Kaneshiro","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"},{"name":"Department of Arrhythmia and Cardiac Pacing Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5574-6617","authenticated-orcid":false,"given":"Akiomi","family":"Yoshihisa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"},{"name":"Department of Clinical Laboratory Sciences Fukushima Medical University School of Health Science Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-4708","authenticated-orcid":false,"given":"Yasuchika","family":"Takeishi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816847116"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12564"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.11.1427"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.8.e32"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.264085"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm1028"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2017.11.004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3230"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11089"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16388-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003199"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11995"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.021101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:57:54Z","timestamp":1715601474000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.021101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,2]]},"references-count":12,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,11,2]]}},"alternative-id":["10.1161\/JAHA.121.021101"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.021101","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,2]]},"assertion":[{"value":"2021-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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