[OP.3A.01] THE COMPARISON OF THE TRANSCRIPTOME PROFILE OF THE AUTONOMOUS AND THE PHYSIOLOGICAL ALDOSTERONE-PRODUCING TISSUE, THE ALDOSTERONE-PRODUCING ADENOMA AND THE ZONA GLOMERULOSA.

OBJECTIVE: Primary aldosteronism (PA) is the most common type of secondary hypertension occurring in ∼10% of hypertensive patients. Up to 50% of PA is caused by aldosterone-producing adenomas (APA). We recently performed a microarray assay using 21 pairs of zona glomerulosa (ZG) and zona fasciculata (ZF), and 14 paired APAs. This study is to identify the potential biological processes and canonical pathways involved with aldosterone regulation, APA formation, or APA and ZG cell functions.

DESIGN AND METHOD: Gene ontology (GO) and pathway analyses were performed on 277 genes differentially expressed in APAs when compared to the physiological aldosterone-producing tissues, ZG samples (Fold-change > 2; P < 0.05); and on 334 genes differentially expressed in ZG when compared to ZF samples (Fold-change > 2; P < 0.05). Comparisons were also made between KCNJ5 genotypes.

RESULTS: The most significantly enriched canonical pathway was NRF2-mediated oxidative stress response in APA vs. ZG (P = 7.87 × 10-5). The main molecular and cell functions of the differentially expressed genes in APA vs. ZG included cell death and survival, cellular growth and proliferation, cellular movement, lipid metabolism and small molecule biochemistry. In ZG vs. ZF, the most significantly enriched canonical pathway of the up-regulated genes was Wnt/β-catenin signaling (P = 2.13 × 10-5) and the most upstream regulating gene was TGFB1 (P = 3.80 × 10-14). The main molecular and cell functions of the differentially expressed genes in ZG vs. ZF included lipid metabolism, small molecule biochemistry, vitamin and mineral metabolism, cell death and survival and molecular transport. The canonical pathways enriched in both APA and ZG, were 'LPS/IL-1 Mediated Inhibition of RXR Function' and 'NRF2-mediated Oxidative Stress Response'. Comparing the genotypes of KCNJ5, two of the top three molecular and cell functions (cellular development, cell death and survival) associated with the differentially expressed genes in KCNJ5 mutant APAs vs. wild-type APAs, were also the top ones in KCNJ5 mutant ZF vs. wild-type ZF.

CONCLUSIONS: A list of genes and canonical pathways which have not been previously documented to have involvement with aldosterone production were found to be differentially expressed or activated. This list could become a useful tool in understanding aldosterone regulation, APA formation, and APA and ZG cell functions.