RESUMO
Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.
Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Hiperaldosteronismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/cirurgia , Aldosterona , Animais , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Humanos , Hiperaldosteronismo/genética , Masculino , Camundongos , Fatores de Transcrição/genéticaRESUMO
PURPOSE OF REVIEW: The aim of this review is to provide an update on the effects of the dietary supplementation with cholesterol-lowering nutraceuticals and nutraceutical combinations affecting vascular function and CV risk in clinical interventional studies. RECENT FINDINGS: Current evidence supports the mild-to-moderate cholesterol-lowering efficacy of red yeast rice, berberine, plant sterols, fibers, and some nutraceutical combinations whereas data on the individual cholesterol-lowering action of other nutraceuticals are either less striking or even inconclusive. There is also promising evidence on the vascular protective effects of some of the aforementioned nutraceuticals. However, except for red yeast rice, clinical interventional studies have not investigated their impact on CV outcomes. Evidence of both cholesterol-lowering and vascular protection is a prerogative of few single nutraceuticals and nutraceutical combinations, which may support their clinical use; however, caution on their uncontrolled adoption is necessary as they are freely available on the market and, therefore, subject to potential misuse.