ArticleClinical epigenetics2022
Whole blood methylome-derived features to discriminate endocrine hypertension.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Molecular pathology of primary aldosteronism and hypercortisolism: Impact on adrenal surgery.iScience · 2026Review
- Emerging methods for subtype differentiation in primary aldosteronism.Journal of internal medicine · 2026Review
- Correlation Between Thyroid Function Parameters and Aldosterone-Renin Ratio in Patients With Primary Aldosteronism and Their Association With Target Organ Damage.International journal of endocrinology · 2026Article
- Renal Hypokalemia: An Endocrine Perspective.The Journal of clinical endocrinology and metabolism · 2024Review
- Pitfalls in the Diagnosis and Management of Hypercortisolism (Cushing Syndrome) in Humans; A Review of the Laboratory Medicine Perspective.Diagnostics (Basel, Switzerland) · 2023Review
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Authors and funding
35 authors at 15 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches.
resultsUnsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods-Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine-predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL.
conclusionsThe blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder.
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