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

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.