Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma

FF Zheng, LM Zhu, AF Nie, XY Li, JR Lin, K Zhang… - …, 2015 - Am Heart Assoc
FF Zheng, LM Zhu, AF Nie, XY Li, JR Lin, K Zhang, J Chen, WL Zhou, ZJ Shen, YC Zhu…
Hypertension, 2015Am Heart Assoc
Recent studies have shown that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and
CACNA1D genes are associated with the pathogenesis of aldosterone-producing adenoma.
Clinical profile and biochemical characteristics of the mutations in Chinese patients with
aldosterone-producing adenoma remain unclear. In this study, we performed DNA
sequencing in 168 Chinese patients with aldosterone-producing adenoma and found 129
somatic mutations in KCNJ5, 4 in ATP1A1, 1 in ATP2B3, and 1 in CACNA1D. KCNJ5 …
Recent studies have shown that somatic mutations in the KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes are associated with the pathogenesis of aldosterone-producing adenoma. Clinical profile and biochemical characteristics of the mutations in Chinese patients with aldosterone-producing adenoma remain unclear. In this study, we performed DNA sequencing in 168 Chinese patients with aldosterone-producing adenoma and found 129 somatic mutations in KCNJ5, 4 in ATP1A1, 1 in ATP2B3, and 1 in CACNA1D. KCNJ5 mutations were more prevalent in female patients and were associated with larger adenomas, higher aldosterone excretion, and lower minimal serum K+ concentration. More interestingly, we identified a novel somatic KCNJ5 mutation (c.445-446insGAA, p.T148-T149insR) that could enhance CYP11B2 mRNA upregulation and aldosterone release. This mutation could also cause membrane depolarization and intercellular Ca2+ increase. In conclusion, somatic KCNJ5 mutations are conspicuously more popular than mutations of other genes in aldosterone-producing adenomas of Chinese patients. The T148-T149insR mutation in KCNJ5 may influence K+ channel selectivity and autonomous aldosterone production.
Am Heart Assoc