Cargando…

Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans

Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methy...

Descripción completa

Detalles Bibliográficos
Autores principales: Beach, Steven R. H., Ong, Mei Ling, Lei, Man-Kit, Carter, Sierra E., Simons, Ronald L., Gibbons, Frederick X., Philibert, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487733/
https://www.ncbi.nlm.nih.gov/pubmed/34533092
http://dx.doi.org/10.1080/15592294.2021.1980688
_version_ 1784792512273055744
author Beach, Steven R. H.
Ong, Mei Ling
Lei, Man-Kit
Carter, Sierra E.
Simons, Ronald L.
Gibbons, Frederick X.
Philibert, Robert A.
author_facet Beach, Steven R. H.
Ong, Mei Ling
Lei, Man-Kit
Carter, Sierra E.
Simons, Ronald L.
Gibbons, Frederick X.
Philibert, Robert A.
author_sort Beach, Steven R. H.
collection PubMed
description Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.
format Online
Article
Text
id pubmed-9487733
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-94877332022-09-21 Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans Beach, Steven R. H. Ong, Mei Ling Lei, Man-Kit Carter, Sierra E. Simons, Ronald L. Gibbons, Frederick X. Philibert, Robert A. Epigenetics Research Paper Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans. Taylor & Francis 2021-10-06 /pmc/articles/PMC9487733/ /pubmed/34533092 http://dx.doi.org/10.1080/15592294.2021.1980688 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Beach, Steven R. H.
Ong, Mei Ling
Lei, Man-Kit
Carter, Sierra E.
Simons, Ronald L.
Gibbons, Frederick X.
Philibert, Robert A.
Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title_full Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title_fullStr Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title_full_unstemmed Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title_short Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans
title_sort methylation of fkbp5 is associated with accelerated dna methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged black americans
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487733/
https://www.ncbi.nlm.nih.gov/pubmed/34533092
http://dx.doi.org/10.1080/15592294.2021.1980688
work_keys_str_mv AT beachstevenrh methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT ongmeiling methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT leimankit methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT cartersierrae methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT simonsronaldl methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT gibbonsfrederickx methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans
AT philibertroberta methylationoffkbp5isassociatedwithaccelerateddnamethylationageingandcardiometabolicriskreplicationinyoungadultandmiddleagedblackamericans