中国原发性醛固酮增多症患者体细胞突变的临床特征
Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma.
作者信息
Zheng Fang-Fang, Zhu Li-Min, Nie Ai-Fang, Li Xiao-Ying, Lin Jing-Rong, Zhang Ke, Chen Jing, Zhou Wen-Long, Shen Zhou-Jun, Zhu Yi-Chun, Wang Ji-Guang, Zhu Ding-Liang, Gao Ping-Jin
机构信息
From the State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.); Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (F.-F.Z., J.-R.L., K.Z., P.-J.G.); Shanghai Institute of Hypertension (F.-F.Z., L.-M.Z., J.C., J.-G.W., D.-L.Z., P.-J.G.), Shanghai Institute of Endocrinology and Metabolism (A.-F.N., X.-Y.L.), and Department of Urology, Ruijin Hospital (W.-L.Z., Z.-J.S.), Shanghai Jiao Tong University School of Medicine, Shanghai, China; and Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China (Y.-C.Z.).
出版信息
Hypertension. 2015 Mar;65(3):622-8. doi: 10.1161/HYPERTENSIONAHA.114.03346. Epub 2015 Jan 26.
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 Ca(2+) 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.
近期研究表明，KCNJ5、ATP1A1、ATP2B3和CACNA1D基因的体细胞突变与醛固酮瘤的发病机制相关。中国醛固酮瘤患者突变的临床特征和生化特性仍不明确。在本研究中，我们对168例中国醛固酮瘤患者进行了DNA测序，发现KCNJ5有129个体细胞突变，ATP1A1有4个，ATP2B3有1个，CACNA1D有1个。KCNJ5突变在女性患者中更常见，且与更大的腺瘤、更高的醛固酮排泄量以及更低的血清最低钾离子浓度相关。更有趣的是，我们鉴定出一种新的体细胞KCNJ5突变（c.445 - 446insGAA，p.T148 - T149insR），它可增强CYP11B2 mRNA上调和醛固酮释放。该突变还可导致膜去极化和细胞间钙离子增加。总之，在中国患者醛固酮瘤中，体细胞KCNJ5突变明显比其他基因突变更常见。KCNJ5中的T148 - T149insR突变可能影响钾离子通道选择性和醛固酮自主分泌。
Zotero 插件