Visinin-Like 1 Is Upregulated in Aldosterone-Producing Adenomas With
            <i>KCNJ5</i>
            Mutations and Protects From Calcium-Induced Apoptosis

Williams, Tracy Ann; Monticone, Silvia; Crudo, Valentina; Warth, Richard; Veglio, Franco; Mulatero, Paolo

doi:10.1161/hypertensionaha.111.188532

Cited by 67 publications

(60 citation statements)

References 21 publications

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“…Reflecting these phenotypes, CYP11B2 mRNA levels were significantly higher in APAs with KCNJ5 mutations than in those without. Although Boulkroun et al found no specific molecular phenotype for APAs with KCNJ5 mutations by the hierarchical clustering of transcriptome profiles from 102 APAs, higher levels of CYP11B2 mRNA in APAs with KCNJ5 mutations, similar to our results, have recently been reported by Wiilaimas et al and more recently by Seccia et al [9,33,34]. The discrepancy between the microarray analysis by Boulkroun et al and the results of the present study and previous findings may be due to ethnic differences and the preciseness of the microarray and qPCR techniques used.…”

Section: Discussionsupporting

confidence: 92%

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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PRIMARY ALDOSTERONISM (PA) has been reported to affect at least 6~10% of patients with essential hypertension [1][2][3][4][5] and is caused mostly by an adrenal adenoma (aldosterone-producing adenoma, APA) or by adrenal hyperplasia (idiopathic hyperaldosteronism, IHA). Although the tumorigenesis of APA remained unclear, somatic mutations of the potassium Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations Abstract. Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e. they had a high frequency of KCNJ5 mutations and exhibited a frequent association with cortisol cosecretion. Therefore, APAs among Japanese patients may have different features from those in Western countries. We added recent cases, examined 47 cases (43% male) of APAs, including clinicopathological features, KCNJ5 mutations, and the mRNA levels of several steroidogenic enzymes, and compared the results obtained to those reported in other countries. While the prevalence of KCNJ5 mutations is approximately 40% in Western countries, 37 APA cases (78.7%) showed mutations: 26 with p.G151R and 11 with p.L168R. Although a significant gender difference has been reported in the frequency of KCNJ5 mutations in Europe, we did not find any gender difference. However, the phenotypes of Japanese patients with mutations were similar to those of patients in Western countries; patients were younger and had higher plasma aldosterone levels, lower potassium levels, and higher diastolic blood pressure. Reflecting these phenotypes, APAs with mutations had higher CYP11B2 mRNA levels. However, in contrast to APAs in Western countries, Japanese APAs with mutations showed lower CYP11B1, CYP17A1, and CYP11A1 mRNA levels. These findings demonstrated that Japanese APA patients may have distinct features including a higher prevalence of KCNJ5 mutations, no gender difference in the frequency of these mutations, and characteristics similar to the zona glomerulosa.

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Section: Discussionsupporting

confidence: 92%

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations

et al. 2017

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“…9 Equivalent transfection rates of rat cDNAs and silencing of HAC15 ATP1A1 were confirmed by real-time TaqMan PCR.…”

Section: Cell Transfection and Gene Silencingmentioning

confidence: 89%

Somatic ATP1A1 , ATP2B3 , and KCNJ5 Mutations in Aldosterone-Producing Adenomas

et al. 2014

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P rimary aldosteronism (PA) is the most common form of secondary hypertension, with a prevalence of 5% to 15% among hypertensive patients and is characterized by the autonomous hypersecretion of aldosterone. Sporadic PA and 3 familial forms (familial hyperaldosteronism types I, II, and III) have been described.1 Sporadic PA accounts for >90% of all cases and is caused by either an aldosterone-producing adenoma (APA), which can be surgically removed, or bilateral adrenal hyperplasia, which is treatable with mineralocorticoid receptor antagonists.Somatic APA mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K + channel 4, GIRK4 (also called the inward rectifier K + channel, Kir3.4), were first identified by Choi et al. 2 Subsequently, Boulkroun et al 3 determined a 34% prevalence of KCNJ5 mutations in a large European cohort of 380 APA. Intriguingly, the KCNJ5 mutations were markedly more prevalent in women, 3 and this predominance was confirmed by successive studies. 4,5 To date, 5 different KCNJ5 mutations causing sporadic PA have been identified, the majority of which are Abstract-Aldosterone-producing adenomas (APAs) cause a sporadic form of primary aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G-protein-activated inward rectifier K + channel 4, GIRK4, account for ≈40% of APAs. Additional somatic APA mutations were identified recently in 2 other genes, ATP1A1 and ATP2B3, encoding Na + /K + -ATPase 1 and Ca 2+ -ATPase 3, respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for mutations in known hotspots for genetic alterations associated with primary aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in 6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations (Na

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“…69 The involvement of the Wnt/␤-catenin pathway in the development of adrenocortical carcinomas is now well established. [72][73][74] The presence of activating mutations in exons 3 and 5 of the CTNNB1 gene, which encodes ␤-catenin, has been described in a wide variety of human cancers, including adrenocortical tumors.…”

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confidence: 99%