Abstract | OBJECTIVE: DESIGN: METHODS: 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. RESULTS: 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's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 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. CONCLUSIONS:
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Authors | Roberta Armignacco, Anne Jouinot, Lucas Bouys, Amandine Septier, Thomas Lartigue, Mario Neou, Cassandra Gaspar, Karine Perlemoine, Leah Braun, Anna Riester, Fidéline Bonnet-Serrano, Anne Blanchard, Laurence Amar, Carla Scaroni, Filippo Ceccato, Gian Paolo Rossi, Tracy Ann Williams, Casper K Larsen, Stéphanie Allassonnière, Maria-Christina Zennaro, Felix Beuschlein, Martin Reincke, Jérôme Bertherat, Guillaume Assié |
Journal | European journal of endocrinology
(Eur J Endocrinol)
Vol. 186
Issue 2
Pg. 297-308
(Jan 13 2022)
ISSN: 1479-683X [Electronic] England |
PMID | 34914631
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers
- Glucocorticoids
- DNA
- Tacrolimus Binding Proteins
- tacrolimus binding protein 5
- Hydrocortisone
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Topics |
- Adolescent
- Adrenal Insufficiency
(blood, genetics)
- Adult
- Aged
- Biomarkers
(blood)
- CpG Islands
(genetics)
- Cushing Syndrome
(blood, genetics)
- DNA
(blood)
- DNA Methylation
(genetics)
- Epigenome
(genetics)
- Female
- Glucocorticoids
(blood, genetics)
- Humans
- Hydrocortisone
(analysis, blood, urine)
- Leukocytes
(chemistry)
- Male
- Middle Aged
- Saliva
(chemistry)
- Tacrolimus Binding Proteins
(genetics)
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