Prevalence and Histopathological Characteristics of KCNJ5 Mutant Aldosterone-Producing Adenomas in a Multi-Ethnic Malaysian Cohort

Research output: Contribution to journalArticle

Abstract

Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.

Original languageEnglish
Article number666
JournalFrontiers in Endocrinology
Volume10
DOIs
Publication statusPublished - 4 Oct 2019

Fingerprint

Zona Fasciculata
Aldosterone
Adenoma
Cytochrome P-450 CYP11B2
Mutation
Immunohistochemistry
Steroids
Staining and Labeling
Hyperaldosteronism
Adrenalectomy
Nonparametric Statistics
DNA Sequence Analysis
Cytoplasm
Genotype
Enzymes

Keywords

  • aldosterone-producing adenomas
  • Asia
  • KCNJ5
  • Malaysia
  • primary aldosteronism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

@article{aed0dc3449ca4c75933fe88f814b06ad,
title = "Prevalence and Histopathological Characteristics of KCNJ5 Mutant Aldosterone-Producing Adenomas in a Multi-Ethnic Malaysian Cohort",
abstract = "Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5{\%}) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.",
keywords = "aldosterone-producing adenomas, Asia, KCNJ5, Malaysia, primary aldosteronism",
author = "Mohideen, {Syahirah Kaja} and Muaatamarulain Mustangin and Kamaruddin, {Nor Azmi} and Rohaizak Muhammad and Jamal, {A. Rahman A.} and Norlela Sukor and Tan, {Geok Chin} and Azizan, {Elena Aisha}",
year = "2019",
month = "10",
day = "4",
doi = "10.3389/fendo.2019.00666",
language = "English",
volume = "10",
journal = "Frontiers in Endocrinology",
issn = "1664-2392",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Prevalence and Histopathological Characteristics of KCNJ5 Mutant Aldosterone-Producing Adenomas in a Multi-Ethnic Malaysian Cohort

AU - Mohideen, Syahirah Kaja

AU - Mustangin, Muaatamarulain

AU - Kamaruddin, Nor Azmi

AU - Muhammad, Rohaizak

AU - Jamal, A. Rahman A.

AU - Sukor, Norlela

AU - Tan, Geok Chin

AU - Azizan, Elena Aisha

PY - 2019/10/4

Y1 - 2019/10/4

N2 - Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.

AB - Studies on excised adrenals from primary aldosteronism patients have found that somatic mutations in KCNJ5 frequently cause excess aldosterone production in the culprit aldosterone-producing adenoma (APA). KCNJ5 mutant APAs were reported to be peculiarly overrepresented among young females and in Oriental cohorts, compared to their older male, or Caucasian counterparts. These larger APAs were also reported to have similarities with the zona fasciculata (ZF) in the adrenal both from the steroid production profile and the morphology of the cell. We therefore aimed to corroborate these findings by characterizing the APAs from a multi-ethnic Malaysian cohort. The prevalence of KCNJ5 mutations was estimated through targeted DNA sequencing of KCNJ5 in 54 APAs. Confirmation of APA sample acquisition was performed by CYP11B2 immunohistochemistry (IHC) staining. The ZF steroid production profile was based on the ZF enzyme CYP17A1 IHC staining, and ZF cell morphology was based on a high cytoplasm to nucleus ratio. Seventeen (31.5%) APAs studied, harbored a KCNJ5 mutation. No female over-representation was seen in this cohort though females were found to have a higher expression of CYP11B2 than males (p = 0.009; Mann-Whitney U test). Age at adrenalectomy correlated negatively with the percentage of ZF-like cells in the APA (p = 0.01; Spearman's rho) but not with the KCNJ5 genotype. KCNJ5 mutant APAs had a high percentage of ZF-like cells (and high CYP17A1 expression) but so did the wild-type APAs. In summary, prevalence of KCNJ5 mutant APAs in this cohort was similar to other Caucasian cohorts, however, over-representation of females did not occur, which is similar to some studies in Oriental cohorts.

KW - aldosterone-producing adenomas

KW - Asia

KW - KCNJ5

KW - Malaysia

KW - primary aldosteronism

UR - http://www.scopus.com/inward/record.url?scp=85073670208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073670208&partnerID=8YFLogxK

U2 - 10.3389/fendo.2019.00666

DO - 10.3389/fendo.2019.00666

M3 - Article

AN - SCOPUS:85073670208

VL - 10

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

M1 - 666

ER -