Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Studies.

Background: Hypertension imposes substantial health and economic burden worldwide. Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, causing cardiovascular events at higher risk compared with essential hypertension. However, the germline genetic contribution to the susceptibility of PA has not been well elucidated.

Association of DNA methylation with steroidogenic enzymes in Cushing's adenoma.

DNA methylation and demethylation regulate the transcription of genes. DNA methylation-associated gene expression of adrenal steroidogenic enzymes may regulate cortisol production in cortisol-producing adenoma (CPA). We aimed to determine the DNA methylation levels of all genes encoding steroidogenic enzymes involved in CPA.

Hypomethylation associated vitamin D receptor expression in ATP1A1 mutant aldosterone-producing adenoma.

DNA methylation alteration is tissue-specific and play a pivotal role in regulating gene transcription during cell proliferation and survival. We aimed to detect genes regulated by DNA methylation, and then investigated whether the gene influenced cell proliferation or survival in adrenal cells. DNA methylation and qPCR analyses were performed in nonfunctioning adrenocortical adenoma (NFA, n = 12) and aldosterone-producing adenoma (APA, n = 35) samples.

Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation.

The molecular mechanisms by which mutation-mediated cell proliferation or tumorigenesis in aldosterone-producing adenomas (APAs) have not been elucidated. First, we investigated whether the APA-associated L104R mutation stimulated cell proliferation. Second, we aimed to clarify the molecular mechanisms by which the mutation-mediated cell proliferated.

Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations.

The intracellular molecular mechanisms underlying the genotype of cortisol-producing adenoma (CPA) have not been fully determined. We analyzed gene expressions in CPA and the human adrenocortical cell line (HAC15 cells) with PRKACA mutation. Clustering analysis using a gene set associated with responses to cAMP revealed the possible differences between PRKACA mutant CPAs and GNAS and CTNNB1 mutant CPAs.

Update on Genetics of Primary Aldosteronism.

Primary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5-10% among patients with hypertension. PA is mainly classified into two subtypes: aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism. Recent developments in genetic analysis have facilitated the discovery of mutations in , , , , , , and in sporadic or familial forms of PA in the last decade.

Angiotensin-converting enzyme 2 expression is not induced by the renin-angiotensin system in the lung.

https://bit.ly/3fkopuO.

Endoplasmic Reticulum Chaperone Calmegin Is Upregulated in Aldosterone-Producing Adenoma and Associates With Aldosterone Production.

The endoplasmic reticulum (ER) plays a pivotal role in syntheses of proteins and steroid hormones and regulation of intracellular Ca level. We aimed to investigate ER-associated genes in aldosterone-producing adenomas (APAs) and clarify their effect on aldosterone production. Microarray analysis targeting 288 ER-associated genes was conducted using nonfunctioning adrenocortical adenomas (n=5) and APAs (n=19).

Measurement of midnight ACTH levels is useful for the evaluation of midnight cortisol levels.

Objective: Elevated midnight cortisol levels induced by non-suppressed ACTH levels may lead to false-positive results for hypercortisolism in patients with adrenal incidentaloma. We investigated whether plasma ACTH-associated high midnight serum cortisol levels are correlated with other endocrinological findings with respect to hypothalamic-pituitaryadrenal function or hypercortisolism status.

Methods: Two-hundred-forty-six patients with adrenocortical adenoma were evaluated via measurements of midnight ACTH and cortisol levels, a 1-mg dexamethasone suppression test (DST), and a cosyntropin-releasing hormone (CRH) stimulation test.

Angiotensin 1-7 suppresses angiotensin II mediated aldosterone production via JAK/STAT signaling inhibition.

Angiotensin 1-7 (Ang 1-7), which is a protein cleaved from angiotensin II (A-II), binds to the MAS receptor. Ang 1-7 has been demonstrated to exert protective effects against A-II-mediated cardiac, atherosclerotic, and renal damages. The aims of our study were to demonstrate the inhibitory role of Ang 1-7 in A-II-mediated aldosterone production by interacting with the MAS receptor in human adrenocortical carcinoma (HAC15) cells, and clarify the intracellular signaling mechanisms underlying the inhibition of aldosterone production by Ang 1-7.

Purkinje Cell Protein 4 Expression Is Associated With DNA Methylation Status in Aldosterone-Producing Adenoma.

Context: Aldosterone production is stimulated by activation of calcium signaling in aldosterone-producing adenomas (APAs), and epigenetic factors such as DNA methylation may be associated with the expression of genes involved in aldosterone regulation.

Objective: Our aim was to investigate the DNA methylation of genes related to calcium signaling cascades in APAs and the association of mutations in genes linked to APAs with DNA methylation levels.

Methods: Nonfunctioning adrenocortical adenoma (n = 12) and APA (n = 35) samples were analyzed.

Calneuron 1 Increased Ca in the Endoplasmic Reticulum and Aldosterone Production in Aldosterone-Producing Adenoma.

Aldosterone production is initiated by angiotensin II stimulation and activation of intracellular Ca signaling. In aldosterone-producing adenoma (APA) cells, the activation of intracellular Ca signaling is independent of the renin-angiotensin-aldosterone systems. The purpose of our study was to clarify molecular mechanisms of aldosterone production related to Ca signaling.

Aberrant G protein-receptor expression is associated with DNA methylation in aldosterone-producing adenoma.

This study aimed to evaluate the methylation levels of G protein-coupled receptor (GPCR) related genes and the effects of methylation on mRNA expression levels in aldosterone-producing adenoma (APA). DNA methylation array and transcriptome analysis were applied in non-functioning adrenocortical adenoma (NFA) and APA. We investigated 192 GPCR-related genes and found hypo-methylation in the promoter region of 66 of these genes in APA.

Association between Serum Elaidic Acid Concentration and Insulin Resistance in Two Japanese Cohorts with Different Lifestyles.

Aim: Many cohort studies have shown that increased trans fatty acid (TFA) intake increases the risk of developing coronary heart disease. However, whether TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown.

Methods: We performed the 75-g oral glucose tolerance test in two Japanese cohorts: a cohort of 454 native Japanese living in Hiroshima, Japan, and a cohort of 426 Japanese-Americans living in Los Angeles, USA, who shared identical genetic predispositions but had different lifestyles.

Hypomethylation of CYP11B2 in Aldosterone-Producing Adenoma.

The purpose of this study was to evaluate the DNA methylation levels of steroidogenic enzyme genes in aldosterone-producing adenoma (APA) and the effects of gene mutations in APA on the DNA methylation levels. DNA methylation array analysis was conducted using nonfunctioning adrenocortical adenoma (n=12) and APA (n=35) samples, including some with a KCNJ5 mutation (n=21), an ATP1A1 mutation (n=5), and without the known mutations (n=9). The quantitative polymerase chain reaction assay was performed for the detection of CYP11B2 and CYP11B1 expression levels in nonfunctioning adrenocortical adenoma and APA.

Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.

We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.