Genetics of Aldosterone-Producing Adenoma in Korean Patients.
Genetics of Aldosterone-Producing Adenoma in Korean Patients.
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DOI：
10.1371/journal.pone.0147590
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kim SY
中科院分区：
文献类型：
--
作者：
Hong AR;Kim JH;Song YS;Lee KE;Seo SH;Seong MW;Shin CS;Kim SW;Kim SY
最近，KCNJ5、ATP1A1、ATP2B3和CACNA1D基因的体细胞突变被发现与醛固酮生成腺瘤（APA）的发病机制有关。本研究旨在调查韩国APA患者KCNJ5、ATP1A1、ATP2B3和CACNA1D体细胞突变的患病率，并研究这些突变与临床和生化特征之间的相关性。我们对66例APA患者进行了靶向基因测序，以检测这些基因的体细胞突变。66例APA患者中有47例（71.2%）出现体细胞KCNJ5突变，其中p.G151R 31例，p.L168R 16例；这两种突变是相互排斥的。未观察到ATP1A1、ATP2B3和CACNA1D基因的体细胞突变。体细胞KCNJ5突变在女性患者中更为普遍（分别为66%和36.8%,P = 0.030）。此外，KCNJ5突变患者在35岁以下患者中所占比例显著高于35岁（分别为19.1%和0%，P = 0.040）。术前血压、血浆醛固酮、血清钾、侧化指数、腺瘤大小根据突变状态无显著差异。与没有突变的患者相比，KCNJ5突变患者在肾上腺切除术后需要降压药物的可能性更低（36.2%比63.2%;P = 0.045）。目前的研究表明，体细胞KCNJ5突变在韩国的APA患者中非常普遍。体细胞KCNJ5突变的携带者多为女性。早期诊断和更好的治疗结果与APA的体细胞KCNJ5突变相关。
Recently, somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes were found to be associated with the pathogenesis of aldosterone-producing adenoma (APA). This study aimed to investigate the prevalence of somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D and examine the correlations between these mutations and the clinical and biochemical characteristics in Korean patients with APA. We performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in these genes. Somatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R); these two mutations were mutually exclusive. Somatic mutations in the ATP1A1, ATP2B3, and CACNA1D genes were not observed. Somatic KCNJ5 mutations were more prevalent in female patients (66% versus 36.8%, respectively; P = 0.030). Moreover, patients with KCNJ5 mutations comprised a significantly higher proportion of patients younger than 35 years of age (19.1% versus 0%, respectively; P = 0.040). There were no significant differences in pre-operative blood pressure, plasma aldosterone, serum potassium, lateralization index, and adenoma size according to mutational status. Patients with KCNJ5 mutations were less likely to need antihypertensive medications after adrenalectomy compared with those without mutation (36.2% versus 63.2%; P = 0.045). The present study demonstrated the high prevalence of somatic KCNJ5 mutations in Korean patients with APA. Carriers of somatic KCNJ5 mutations were more likely to be female. Early diagnosis and better therapeutic outcomes were associated with somatic KCNJ5 mutations in APA.