Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway

Arnesen, Thomas; Glomnes, Nina; Strømsøy, Siri S.; Knappskog, Stian; Heie, Anette; Akslen, Lars A.; Grytaas, Marianne Aardal; Varhaug, Jan Erik; Gimm, Oliver; Brauckhoff, Michael

doi:10.1007/s00423-013-1093-2

Cited by 33 publications

(26 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All mutation‐positive patients had confirmed APAs on histopathology, with two patients having associated background hyperplasia. These findings are in concordance with other large series, which demonstrate that mutations in KCNJ5 are confined to patients with APA . Overall tumour prevalence of 41% is in line with other larger series .…”

Section: Discussionsupporting

confidence: 93%

“…A recent landmark article by Choi and colleagues identified somatic mutations (G151R and L168R) in the KCNJ5 gene that affected the Kir3.4 potassium channel found in the ZG . Subsequent studies have also confirmed the presence of these somatic mutation in up to 45% of patients with APAs . Interestingly, germ line mutations (G151E) in KCNJ5 have also been noted in patients with familial hyperaldosteronism type III …”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Mutations in KCNJ5 determines presentation and likelihood of cure in primary hyperaldosteronism

Pang

Pon

et al. 2013

ANZ Journal of Surgery

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 97%

Mutations in KCNJ5 determines presentation and likelihood of cure in primary hyperaldosteronism

Pang

Pon

et al. 2013

ANZ Journal of Surgery

View full text Add to dashboard Cite

show abstract

“…The total prevalence of KCNJ5 somatic mutations in APAs was 65.2% in a Japanese report [10], 76.8% in a Chinese report [11] and 59.5% in a Taiwanese report [12]. Evidence showed KCNJ5 -mutant carriers were younger, had higher levels of preoperative aldosterone, more severe hypokalemia, and had a better hypertension prognosis after adrenalectomy than non-mutant carriers [9, 12–14]. Although it is well known that primary aldosteronism increases cardiovascular risk [15, 16], we are interested in knowing whether KCNJ5 -mutant carriers have a higher risk of cardiovascular damage than non-mutant carriers.…”

Section: Introductionmentioning

confidence: 99%

Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring KCNJ5 mutations after adrenalectomy

Chang

Tsai

et al. 2017

Oncotarget

View full text Add to dashboard Cite

The aim of this study was to show the effect of KCNJ5 mutational status on arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between February 2008 and January 2010, we prospectively enrolled 108 aldosterone-producing adenoma patients undergoing adrenalectomy. We conducted repeated measurements of pulse wave velocity at baseline, 6 months, and 12 months after adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial stiffness and risk for hypertension at 12 months after adrenalectomy were analyzed after propensity score matching in a 1:1 ratio. After matching for age, sex and body mass index, 88 patients were divided equally into KCNJ5-mutant and non-mutant groups. KCNJ5 mutational status was not an independent variable in either the generalized estimating equation model (p = 0.147) or the percentage change of brachial-ankle pulse wave velocity (p = 0.106). The generalized additive model smoothing plot showed that aldosterone-producing adenoma patients who carried the KCNJ5 mutation and were aged between 37 and 60 may have a hypertension recovery advantage. According to our observations during a 12-month follow-up after adrenalectomy, KCNJ5 mutational status was not associated with improvement in arterial stiffness.

show abstract

“…15 Currently, there has not been agreement on the correlation between KCNJ5 mutations and response to adrenalectomy. 15,16 Therefore, a greater number of cases need to be studied to evaluate the clinical characteristics of patients with and without somatic mutations in APAs. There has been no study investigating somatic mutations in APAs in China thus far.…”

mentioning

confidence: 99%

Clinical Characteristics of Somatic Mutations in Chinese Patients With Aldosterone-Producing Adenoma

et al. 2015

View full text Add to dashboard Cite

Recent studies have shown that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are associated with the pathogenesis of aldosterone-producing adenoma. Clinical profile and biochemical characteristics of the mutations in Chinese patients with aldosterone-producing adenoma remain unclear. In this study, we performed DNA sequencing in 168 Chinese patients with aldosterone-producing adenoma and found 129 somatic mutations in KCNJ5, 4 in ATP1A1, 1 in ATP2B3, and 1 in CACNA1D. KCNJ5 mutations were more prevalent in female patients and were associated with larger adenomas, higher aldosterone excretion, and lower minimal serum K + concentration. More interestingly, we identified a novel somatic KCNJ5 mutation (c.445-446insGAA, p.T148-T149insR) that could enhance CYP11B2 mRNA upregulation and aldosterone release. This mutation could also cause membrane depolarization and intercellular Ca 2+ increase. In conclusion, somatic KCNJ5 mutations are conspicuously more popular than mutations of other genes in aldosterone-producing adenomas of Chinese patients. The T148-T149insR mutation in KCNJ5 may influence K + channel selectivity and autonomous aldosterone production.

show abstract

Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway

Abstract: KCNJ5 mutations are associated with a better surgical outcome. Preoperative identification of the mutation status might have impact on surgical strategy (total vs. subtotal adrenalectomy).

Cited by 33 publications

References 21 publications

Mutations in KCNJ5 determines presentation and likelihood of cure in primary hyperaldosteronism

Mutations in KCNJ5 determines presentation and likelihood of cure in primary hyperaldosteronism

Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring KCNJ5 mutations after adrenalectomy

Clinical Characteristics of Somatic Mutations in Chinese Patients With Aldosterone-Producing Adenoma

Contact Info

Product

Resources

About