{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:23:30Z","timestamp":1790821410142,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Cushing\u2019s syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing\u2019s syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing\u2019s syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing\u2019s syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing\u2019s syndrome correction. In Cushing\u2019s syndrome, an enrichment in hypomethylated CpG sites was observed in the region of <jats:italic>FKBP5<\/jats:italic> gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0907","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T19:27:01Z","timestamp":1639682821000},"page":"297-308","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":19,"title":["Identification of glucocorticoid-related molecular signature by whole blood methylome analysis"],"prefix":"10.1093","volume":"186","author":[{"given":"Roberta","family":"Armignacco","sequence":"first","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Jouinot","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Bouys","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Septier","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lartigue","sequence":"additional","affiliation":[{"name":"2ARAMIS Project-Team, Inria Paris, France"},{"name":"3CMAP, UMR 7641, CNRS, \u00c9cole polytechnique, I.P. Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Neou","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Gaspar","sequence":"additional","affiliation":[{"name":"4Sorbonne Universit\u00e9, Inserm, UMS Pass, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re, P3S, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Perlemoine","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Braun","sequence":"additional","affiliation":[{"name":"5Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Riester","sequence":"additional","affiliation":[{"name":"5Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fid\u00e9line","family":"Bonnet-Serrano","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"},{"name":"6Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Service d\u2019Hormonologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Blanchard","sequence":"additional","affiliation":[{"name":"7Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Centre d\u2019Investigations Cliniques 9201, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Amar","sequence":"additional","affiliation":[{"name":"8Universit\u00e9 de Paris, PARCC, INSERM, Paris, France"},{"name":"9Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Unit\u00e9 Hypertension Art\u00e9rielle, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Scaroni","sequence":"additional","affiliation":[{"name":"10UOC Endocrinologia, Dipartimento di Medicina DIMED, Azienda Ospedaliera-Universit\u00e0 di Padova, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[{"name":"10UOC Endocrinologia, Dipartimento di Medicina DIMED, Azienda Ospedaliera-Universit\u00e0 di Padova, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-0931","authenticated-orcid":true,"given":"Gian Paolo","family":"Rossi","sequence":"additional","affiliation":[{"name":"11Clinica dell\u2019Ipertensione Arteriosa, Department of Medicine-DIMED, University of Padua, Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy Ann","family":"Williams","sequence":"additional","affiliation":[{"name":"12Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper K","family":"Larsen","sequence":"additional","affiliation":[{"name":"8Universit\u00e9 de Paris, PARCC, INSERM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Allassonni\u00e8re","sequence":"additional","affiliation":[{"name":"13CRC, UMR S1138, Universit\u00e9 de Paris, INSERM, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Christina","family":"Zennaro","sequence":"additional","affiliation":[{"name":"8Universit\u00e9 de Paris, PARCC, INSERM, Paris, France"},{"name":"14Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3984","authenticated-orcid":true,"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"5Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"},{"name":"15Klinik f\u00fcr Endokrinologie, Diabetologie und Klinische Ern\u00e4hrung, Universit\u00e4tsSpital Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"5Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bertherat","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"},{"name":"16Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Service d\u2019Endocrinologie, Center for Rare Adrenal Diseases, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Assi\u00e9","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France"},{"name":"16Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Cochin, Service d\u2019Endocrinologie, Center for Rare Adrenal Diseases, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/186\/2\/EJE-21-0907.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/186\/2\/EJE-21-0907.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:17:19Z","timestamp":1676391439000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/186\/2\/297\/6852982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,1]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0907","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,1]]}}}