ArticleEndocrine2016
Reduced DNA methylation of FKBP5 in Cushing's syndrome.
Article in Endocrine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- DNA methylation and brain structure and function across the life course: A systematic review.Neuroscience and biobehavioral reviews · 2020Pooled it
- The aging paradox of Cushing's syndrome: Stress without clear senescence?Journal of neuroendocrinology · 2026Review
- Steroid alterations in Cushing's disease persist after remission: ACTH-driven steroid changes dissociate from mood-regulatory neurosteroids.Frontiers in endocrinology · 2026Article
- A Cross-Generational Methylomic Signature of Infant Maltreatment in Newborn Rhesus Macaques.Biological psychiatry · 2025Article
- Current Challenges and Future Directions in the Assessment of Glucocorticoid Status.Endocrine reviews · 2024Review
- Epigenetic Mechanisms Modulated by Glucocorticoids With a Focus on Cushing Syndrome.The Journal of clinical endocrinology and metabolism · 2024Review
- Blood DNA methylation ofFrontiers in epigenetics and epigenomics · 2024Article
- Glucocorticoids and cognitive function: a walkthrough in endogenous and exogenous alterations.Journal of endocrinological investigation · 2023Review
- Review
- Oxidative Stress and Nuclear Reprogramming: A Pilot Study of the Effects of Reactive Oxygen Species on Architectural and Epigenetic Landscapes.International journal of molecular sciences · 2022Article
- A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity.Scientific reports · 2022Article
- Identification of glucocorticoid-related molecular signature by whole blood methylome analysis.European journal of endocrinology · 2022Article
- Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside.International journal of molecular sciences · 2022Review
- Cross-species Association Between Telomere Length and Glucocorticoid Exposure.The Journal of clinical endocrinology and metabolism · 2021Article
- Associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in systemic lupus erythematosus patients.Clinical rheumatology · 2021Article
- The Effects of Early Life Stress on the Brain and Behaviour: Insights From Zebrafish Models.Frontiers in cell and developmental biology · 2021Review
- DNA methylation of FKBP5 in South African women: associations with obesity and insulin resistance.Clinical epigenetics · 2020Article
- Focus on FKBP51: A molecular link between stress and metabolic disorders.Molecular metabolism · 2019Review
- Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.Clinical epigenetics · 2019Article
- Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma.Frontiers in psychiatry · 2019Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.