Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas

Azizan, Elena A.B., Murthy, Meena, Stowasser, Michael, Gordon, Richard, Kowalski, Bartosz, Xu, Shengxin, Brown, Morris J. and O'Shaughnessy, Kevin M. (2012) Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. Hypertension, 59 3: 587-591. doi:10.1161/HYPERTENSIONAHA.111.186239


Author Azizan, Elena A.B.
Murthy, Meena
Stowasser, Michael
Gordon, Richard
Kowalski, Bartosz
Xu, Shengxin
Brown, Morris J.
O'Shaughnessy, Kevin M.
Title Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas
Journal name Hypertension   Check publisher's open access policy
ISSN 0194-911X
1524-4563
Publication date 2012-03
Sub-type Article (original research)
DOI 10.1161/HYPERTENSIONAHA.111.186239
Volume 59
Issue 3
Start page 587
End page 591
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2013
Language eng
Abstract Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium channel, are present in some sporadic nonsyndromic APAs. To address this further we screened 2 large collections of sporadic APAs from the United Kingdom and Australia (totalling 73) and found somatic mutations in the selectivity filter of KCNJ5 in 41% (95% CI: 31% to 53%) of the APAs (30 of 73). These included the previously noted nonsynonymous mutations, G151R and L158R, and an unreported 3-base deletion, delI157, in the region of the selectivity filter. APAs containing a somatic KCNJ5 mutation were significantly larger than those without (1.61 cm [95% CI: 1.39-1.83 cm] versus 1.04 cm [95% CI: 0.91-1.17 cm]; P<0.0001) but with substantial overlap in size between genotypes. The APAs carrying a mutation, but not those without, also consistently lacked a postural aldosterone response, suggesting a physiologically distinct subtype. Hence, somatic KCNJ5 mutations are not restricted to large APAs (>2 cm), and their frequency in our unselected series suggests they are common and could be important in the molecular pathogenesis of many sporadic cases of APA.
Keyword Hyperaldosteronism
Hypertension
Potassium channels
Kcnj5
Aldosterone-producing adenoma
Posture response
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 17 January 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 71 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 85 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 16 Apr 2012, 13:04:56 EST by System User on behalf of Medicine - Princess Alexandra Hospital