**7. Influence of Genetics and Genomics on Surgical Outcome**

High blood pressure may persist after adrenalectomy due to contributory factors other than PA and the surgical cure rate of patients with APAs varies widely. Comparison of the transcriptomes of APAs with normal adrenals identified two subgroups of APAs based on their expression profiles (low *versus* high mRNA levels) of genes encoding steroidogenic enzymes. APAs with a low level of

*CYP11B2* gene transcription are associated with a longer known duration of hypertension and a lower rate of long-term cure [43].

Microarray analysis identified differentially expressed genes in a comparison of the transcriptomes of APAs from patients with persistent hypertension after adrenalectomy with that of patients with APA who were cured by surgery [75]. The differentially expressed genes were associated with five different pathways that included lipid metabolism and cell differentiation and indicate the possibility of using genomic approaches to identify drug targets and prognostic markers [75].

A number of studies have investigated the effect of *KCNJ5* mutational status as a marker for surgical outcome. In a prospective study by the TAIPAI (Taiwan Primary Aldosteronsim Investigation study group) of 108 patients that were divided into *KCNJ5* mutated and non-mutated groups, patients with an APA carrying a *KCNJ5* mutation aged between 37 and 60 years may have an advantage in blood pressure response to surgery but mutation status is not associated with an improvement in arterial stiffness [76].

Cardiovascular complications before and after unilateral adrenalectomy in patients harboring APAs with and without *KCNJ5* gene mutations were evaluated in a Japanese population. The *KCNJ5*-mutated group displayed a significant improvement in left ventricular mass index which was independently associated with the presence of APA *KCNJ5* mutations whereas the group without *KCNJ5* mutations had no such improvement [77]. A higher left ventricular mass index and plasma aldosterone concentration in patients with APA *KCNJ5* mutations relative to those without *KCNJ5* mutations has also been reported [35]. Despite the increased cardiac damage, patients with *KCNJ5* mutations exhibited a decrease of blood pressure and plasma aldosterone concentrations and a regression of left ventricular mass index similar to the *KCNJ5* wild type group after adrenalectomy [35]. Another study reported an association of APA *KCNJ5* mutations with lower blood pressure and the higher likelihood of cure of PA by adrenalectomy relative to patients with APA without *KCNJ5* mutations [36].
