KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness

Abstract

Primary aldosteronism is the most common form of secondary hypertension and induces various cardiovascular injuries. In aldosterone-producing adenoma (APA), the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of confounding factors is uncertain. We enrolled 213 APA patients who were scheduled to undergo adrenalectomy. KCNJ5 gene sequencing of APA was performed. After propensity score matching (PSM) for age, sex, body mass index, blood pressure, number of hypertensive medications, and hypertension duration, there were 66 patients in each group with and without KCNJ5 mutations. The mutation carriers had a higher aldosterone level and lower log transformed brachial–ankle pulse wave velocity (baPWV) than the non-carriers before PSM, but no difference in log baPWV after PSM. One year after adrenalectomy, the mutation carriers had greater decreases in log plasma aldosterone concentration, log aldosterone–renin activity ratio, and log baPWV than the non-carriers after PSM. Only the mutation carriers had a significant decrease in log baPWV after surgery both before and after PSM. KCNJ5 mutations were not correlated with baseline baPWV after PSM but were significantly correlated with ∆baPWV after surgery both before and after PSM. Conclusively, APA patients with KCNJ5 mutations had a greater regression in arterial stiffness after adrenalectomy than those without mutations.

Synergistic effect of albuminuria on atherosclerosis in patients with primary aldosteronism

“…29 Genetically, the somatic mutation KCNJ5 has been shown to predict greater recovery of arterial stiffness after adrenalectomy. 30 Few studies have investigated the role of concomitant albuminuria on the progression of atherosclerosis. In this study, we investigated the role of albuminuria on arterial stiffness in PA patients at baseline and after PA-targeted treatment.…”

“… 29 Genetically, the somatic mutation KCNJ5 has been shown to predict greater recovery of arterial stiffness after adrenalectomy. 30 …”

Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

“…We previously found that KCNJ5 somatic mutations were predominant in patients with APA harboring somatic mutations [ KCNJ5 accounts for 90.6% of APA patients with somatic mutations ( 39 ) detected by traditional methods, 81.2% of APA patients with somatic mutations by sequencing combined with Sanger and IHC-guided biopsy and NGS ( 55 )]. Besides, the majority of studies investigating the clinical impacts of somatic mutations in APA patients are almost limited to comparing “ KCNJ5 mutations” with “non- KCNJ5 mutations” ( 40 , 41 , 46 , 48 , 57 – 60 ). The clinical data of other somatic mutations in APA patients is rare.…”

“…A recent study ( 60 ) revealed lower brachial-ankle PWV (baPWV) in patients with KCNJ5 mutations compared to those without mutations before propensity score matching (PSM), but similar baPWV in both patients with and without mutations after matching for age, sex, BMI and hypertension status. After adrenalectomy, the decrease in baPWV in APA patients with KCNJ5 mutations was greater than that in those without mutations both before and after PSM.…”

New Insights in the Genetics and Genomics of Adrenocortical Tumors and Pheochromocytomas

“…Recent studies have shown that a significant proportion of aldosterone-producing adrenocortical adenomas harbor somatic mutations in a subset of genes mostly coding ion channels. The disease phenotype might be associated with some genetic variants, as the article by Chang et al shows greater recovery from arterial stiffness in adenomas harboring KCNJ5 somatic mutations [ 1 ]. The molecular features of a novel mutation in the ATP2B3 gene are presented in detail in the article by Liao et al [ 2 ].…”