The relationship between tissue inhibitor of metalloproteinases-1 and KCNJ5 mutation in aldosterone-producing adenoma patients

No-Ting Lin; Tsung-Yan Chen; Xue-Ming Wu; Yi-Yao Chang; Cheng-Hsuan Tsai; Che-Wei Liao; Tai-Shuan Lai; Chin-Chen Chang; Bo-Ching Lee; Ching-Chu Lu; Jeff Shih-Chieh Chueh; Vin-Cent Wu; Chi-Sheng Hung; Zheng-Wei Chen; Yen-Hung Lin; TAIPAI Study Group

doi:10.1038/s41440-024-02030-w

The relationship between tissue inhibitor of metalloproteinases-1 and KCNJ5 mutation in aldosterone-producing adenoma patients

Hypertens Res. 2024 Dec 17. doi: 10.1038/s41440-024-02030-w. Online ahead of print.

Authors

No-Ting Lin¹, Tsung-Yan Chen^{2

3}, Xue-Ming Wu⁴, Yi-Yao Chang^{5

6}, Cheng-Hsuan Tsai^{3

7}, Che-Wei Liao^{3

8}, Tai-Shuan Lai³, Chin-Chen Chang⁹, Bo-Ching Lee⁹, Ching-Chu Lu¹⁰, Jeff Shih-Chieh Chueh¹¹, Vin-Cent Wu³, Chi-Sheng Hung³, Zheng-Wei Chen^{12

13

14}, Yen-Hung Lin³; TAIPAI Study Group

Collaborators

Affiliations

¹ Department of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC.
² Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan, ROC.
³ Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
⁴ Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan, ROC.
⁵ Department of Cardiovascular Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC.
⁶ Graduate Institute of Medicine, Yuan Ze University, Taoyuan City, Taiwan, ROC.
⁷ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
⁸ Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan, ROC.
⁹ Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹⁰ Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.
¹¹ Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹² Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC. librajohn7@hotmail.com.
¹³ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. librajohn7@hotmail.com.
¹⁴ Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan, ROC. librajohn7@hotmail.com.

PMID: 39690251
DOI: 10.1038/s41440-024-02030-w

Abstract

KCNJ5 somatic mutations in aldosterone-producing adenoma (APA) are linked to higher left ventricular mass index (LVMI) and worse diastolic function. We previously identified an association between plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and an aldosterone-induced increase in LVMI and diastolic dysfunction. This study aimed to investigate the association between the presence of KCNJ5 somatic mutation and plasma TIMP-1 in APA patients. We enrolled 60 APA patients undergoing adrenalectomy, including 30 with KCNJ5 mutations (KCNJ5(+)) and 30 without (KCNJ5(-)). Clinical characteristics, echocardiographic data (including LVMI, inappropriately excessive LVMI (ieLVMI), and diastolic function) and plasma TIMP-1 levels were measured before surgery and 1 year postoperatively. The results showed that the KCNJ5(+) group had higher plasma TIMP-1 levels (P = 0.004) compared to the KCNJ5(-) group. The correlation between the KCNJ5 mutations and TIMP-1 levels remained significant after multiple regression analysis. To detect KCNJ5 mutations, receiver operating characteristic curve analysis showed TIMP-1 had the best area under the curve (AUC) value among various clinical parameters (AUC = 0.682, 95% confidence interval = 0.549-0.796, P = 0.008). Post-adrenalectomy, only the KCNJ5(+) group showed significant decrease in LVMI (P = 0.001) and log-transformed TIMP-1 levels (P = 0.035). Changes in ieLVMI before and after surgery were consistently correlated with changes in TIMP-1 levels in multivariable regression analysis. In conclusion, KCNJ5 somatic mutations in APA are associated with higher plasma TIMP-1 levels. In addition, TIMP-1 is an effective biomarker for detecting the presence of KCNJ5 mutations in APA patients.

Keywords: Aldosterone-producing adenoma; KCNJ5 somatic mutation; Myocardial fibrosis; Primary aldosteronism; Tissue inhibitor of metalloproteinases-1.