Genetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene

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dc.contributor.authorFardella, CE
dc.contributor.authorPinto, M
dc.contributor.authorMosso, L
dc.contributor.authorGomez Sanchez, C
dc.contributor.authorJalil, J
dc.contributor.authorMontero, J
dc.date.accessioned2024-01-10T13:13:16Z
dc.date.available2024-01-10T13:13:16Z
dc.date.issued2001
dc.description.abstractGlucocorticoid-remediable aldosteronism is an inherited disorder caused by a chimeric gene duplication between the CYP11B1 (11 beta -hydroxylase) and CYP11B2 (aldosterone synthase) genes. The disorder is characterized by hyperaldosteronism and high levels of 18-hydroxycortisol and 18-oxocortisol, which are under ACTH control. The diagnosis of glucocorticoid-remediable aldosteronism had been traditionally made using the dexamethasone suppression test; however, recent studies have shown that several patients with primary aldosteronism and a positive dexamethasone suppression test do not have the chimeric CYP11B1/CYP11B2 gene. The aim of this work was to evaluate whether other genetic alterations exist in CYP11B genes (gene conversion in the coding region of CYP11B1 or in the promoter of CYP11B2) that could explain a positive dexamethasone suppression test and to determine another genetic cause of glucocorticoid-remediable aldosteronism. We also evaluated the role of 18-hydroxycortisol. as a specific biochemical marker of glucocorticoid-remediable aldosteronism. We studied eight patients with idiopathic hyperaldosteronism, a positive dexamethasone suppression test, and a negative genetic test for the chimeric gene. In all patients we amplified the CYP11B1 gene by PCR and sequenced exons 3-9 of CYP11B1 and a specific region (-138 to -284) of CYP11B2 promoter. We also measured the levels of 18-hydroxycortisol, and we compared the results with those found in four subjects with the chimeric gene. None of eight cases showed abnormalities in exons 3-9 of CYP11B1, disproving a gene conversion phenomenon. In all patients a fragment of 393 bp corresponding to a specific region of the promoter of CYP11B2 gene was amplified. The sequence of the fragment did not differ from that of the wild-type promoter of the CYP11B2 gene. The 18-hydroxycortisol levels in the eight idiopathic hyperaldosteronism patients and four controls with chimeric gene were 3.9 +/- 2.3 and 21.9 +/- 3.5 nmol/liter, respectively (P < 0.01). In summary, we did not find other genetic alterations or high levels of 18-hydroxycortisol that could explain a positive dexamethasone suppression test in idiopathic hyperaldosteronism. We suggest that the dexamethasone suppression test could lead to an incorrect diagnosis of glucocorticoid-remediable aldosteronism.
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderNHLBI NIH HHS
dc.fechaingreso.objetodigital2024-05-15
dc.format.extent3 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1210/jc.86.10.4805
dc.identifier.issn0021-972X
dc.identifier.pubmedidMEDLINE:11600544
dc.identifier.urihttps://doi.org/10.1210/jc.86.10.4805
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78287
dc.identifier.wosidWOS:000171755400040
dc.information.autorucMedicina;Fardella C;S/I;66235
dc.information.autorucMedicina;Jalil J;S/I;99946
dc.information.autorucMedicina;Montero J;S/I;98797
dc.information.autorucMedicina;Mosso L;S/I;88201
dc.issue.numero10
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final4807
dc.pagina.inicio4805
dc.publisherENDOCRINE SOC
dc.revistaJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
dc.rightsacceso restringido
dc.subjectGLUCOCORTICOID-REMEDIABLE ALDOSTERONISM
dc.subjectII DEFICIENCY
dc.subjectHYPERALDOSTERONISM
dc.subject18-OXOCORTISOL
dc.subjectCYP11B1
dc.subject18-HYDROXYCORTISOL
dc.subjectCONVERSION
dc.subjectCORTISOL
dc.subjectMUTATION
dc.subjectADENOMA
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGenetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene
dc.typeartículo
dc.volumen86
sipa.codpersvinculados66235
sipa.codpersvinculados99946
sipa.codpersvinculados98797
sipa.codpersvinculados88201
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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