Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche

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dc.contributor.authorPonce, Diana
dc.contributor.authorRodríguez, Fernando
dc.contributor.authorMiranda, José Patricio
dc.contributor.authorBinder, Alexandra M.
dc.contributor.authorSantos Martín, José Luis
dc.contributor.authorMichels, Karin B.
dc.contributor.authorCutler, Gordon B.
dc.contributor.authorPereira, Ana
dc.contributor.authorÍñiguez, Germán
dc.contributor.authorMericq, Verónica
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.departmentInstitute on Innovation and Sustainable Development in Food Chain - ISFOODen
dc.date.accessioned2025-04-14T10:20:55Z
dc.date.available2025-04-14T10:20:55Z
dc.date.issued2023-04-13
dc.date.updated2025-04-14T10:14:10Z
dc.description.abstractBiochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.en
dc.description.sponsorshipThis work was supported by the National Research and Development Agency through the Regular Fondecyt Project N° 1140447 and 1190346 to Dr. Verónica Mericq; the Regular Fondecyt Project N° 1120326 to Dr. Camila Corvalán; and the Regular Fondecyt Project N° 1150416 to José L. Santos and the R01 grant (R01CA158313) to Karin B. Michels.
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/vnd.ms-excelen
dc.identifier.citationPonce, D., Rodríguez, F., Miranda, J. P., Binder, A. M., Santos, J. L., Michels, K. B., Cutler, G. B., Pereira, A., Iñiguez, G., Mericq, V. (2023). Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche. Epigenetics, 18(1), 1-12. https://doi.org/10.1080/15592294.2023.2200366.
dc.identifier.doi10.1080/15592294.2023.2200366
dc.identifier.issn1559-2308
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/53975
dc.language.isoeng
dc.publisherTaylor & Francis
dc.relation.ispartofEpigenetics (2023), vol. 18, núm. 1, 2200366
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/PT17%2F0019/
dc.relation.publisherversionhttps://doi.org/10.1080/15592294.2023.2200366
dc.rights© 2023 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectPremature adrenarcheen
dc.subjectDHEASen
dc.subjectMethylationen
dc.subjectGlucose metabolismen
dc.titleDifferential methylation pattern in pubertal girls associated with biochemical premature adrenarcheen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationa52c0775-f788-4e86-bfbb-a94121c2fbd4
relation.isAuthorOfPublication.latestForDiscoverya52c0775-f788-4e86-bfbb-a94121c2fbd4

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