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

Authors

  • Julian C. Y. Ip,

    Corresponding author
    1. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
    • Correspondence

      Dr Julian C. Y. Ip, L9 Kolling Institute, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. Email: julianip@yahoo.com

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  • Tony C. Y. Pang,

    1. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
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  • Cindy K. Pon,

    1. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
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  • Jing Ting Zhao,

    1. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
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  • Mark S. Sywak,

    1. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
    2. Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
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  • Anthony J. Gill,

    1. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
    2. Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia
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  • Patsy S. Soon,

    1. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
    3. South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
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  • Stan B. Sidhu

    1. Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
    2. Faculty of Medicine, Northern Clinical School, The University of Sydney, Sydney, New South Wales, Australia
    3. Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, New South Wales, Australia
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  • Julian C. Y. Ip is a holder of a RACS Sir Roy McCaughey Research Scholarship.
  • J. C. Y. Ip MBBS, BMedSc (Hons); T. C. Y. Pang MS MBiostat, FRACS; C. K. Pon PhD; J. T. Zhao PhD; M. S. Sywak FRACS; A. J. Gill FRCPA; P. S. Soon FRACS, PhD; S. B. Sidhu FRACS, PhD.

Abstract

Introduction

Primary hyperaldosteronism (PA) is a common cause of secondary hypertension. Two recurrent mutations (G151R and L168R) in the potassium channel gene KCNJ5 have been identified that affect the Kir3.4 potassium channel found in the cells of the zona glomerulosa of the adrenal gland. The aim of this study was to determine the prevalence of KCNJ5 mutations in an Australian cohort of patients and to correlate these findings with clinical outcome data, in order to describe the clinical impact on patients who harbour this mutation.

Methods

Direct Sanger sequencing for KCNJ5 on DNA from adrenal tumour tissue of 83 patients with PA in a cohort study was undertaken and mutation status correlated with clinical outcome data.

Results

Seventy-one of 83 patients (86%) had adrenocortical adenomas and 12 patients (14%) had bilateral adrenal hyperplasia. A total of 34 (41%) patients were found to have heterozygous somatic mutations in KCNJ5, G151R and L168R. No germ line mutations were identified. Patients with mutations were predominately female (68% versus 49%) and significantly younger at presentation (48 versus 55 years). When correlated with clinical data, our results demonstrated that patients with KCNJ5 mutations were more likely to be cured following surgery without the requirement for ongoing medications.

Conclusions

Our findings in a large Australian cohort show that patients with mutations in KCNJ5 present earlier with the signs and symptoms of PA benefit from surgical intervention. Moreover, our results highlight the importance of a thorough workup and management plan for younger patients who present with hypertension.

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