Prevalence, Clinical, and Molecular Correlates of KCNJ5 Mutations in Primary Aldosteronism
Prevalence, Clinical, and Molecular Correlates of KCNJ5 Mutations in Primary Aldosteronism
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DOI：
10.1161/hypertensionaha.111.186478
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发表时间：
2012-03-01
期刊：
影响因子：
8.3
通讯作者：
Zennaro, Maria-Christina
中科院分区：
文献类型：
--
作者：
Boulkroun, Sheerazed;Beuschlein, Felix;Zennaro, Maria-Christina
原发性醛固酮增多症是继发性高血压最常见的形式。KCNJ 5基因突变最近在醛固酮腺瘤（APA）中被描述。本研究的目的是调查原发性醛固酮增多症患者中KCNJ 5突变的患病率及其临床、生物学和分子相关性。对原发性醛固酮增多症患者的体细胞（阿帕，n = 380）和外周（阿帕，n = 344;双侧肾上腺增生，n = 174）DNA进行KCNJ 5测序，通过欧洲肾上腺肿瘤研究网络收集。在102个肿瘤中进行转录组分析。阿帕中有129例（34%）存在KCNJ 5突变（p.Gly151Arg或p.Leu168Arg）。女性（49%）的患病率明显高于男性（19%; P < 10（-3））和年轻患者（42.1 +/- 1.0 vs 47.6 +/- 0.7岁; P < 10（-3）），并与术前较高的醛固酮水平相关（455 +/- 26 vs 376 +/- 17 ng/L; P = 0.012），但与术后治疗结局无关。在阿帕和双侧肾上腺皮质增生患者中均未发现KCNJ 5基因突变。体细胞KCNJ 5突变是阿帕的特异性突变，因为在25例瘤周肾上腺组织或16例皮质醇腺瘤中未发现。转录组谱的层次聚类显示，具有p.Gly151Arg或p.Leu168Arg突变的APA与没有KCNJ 5突变的肿瘤难以区分。总之，尽管大部分散发性APA携带体细胞KCNJ 5突变，但生殖系突变对双侧肾上腺增生的致病性并不相似。KCNJ 5突变携带者更可能是女性;诊断时年龄较小和醛固酮水平较高表明KCNJ 5突变可能与原发性醛固酮增多症的更华丽表型相关。（高血压。2012; 59：592-598）。在线补充资料
Primary aldosteronism is the most common form of secondary hypertension. Mutations in the KCNJ5 gene have been described recently in aldosterone-producing adenomas (APAs). The aim of this study was to investigate the prevalence of KCNJ5 mutations in unselected patients with primary aldosteronism and their clinical, biological and molecular correlates. KCNJ5 sequencing was performed on somatic (APA, n = 380) and peripheral (APA, n = 344; bilateral adrenal hyperplasia, n = 174) DNA of patients with primary aldosteronism, collected through the European Network for the Study of Adrenal Tumors. Transcriptome analysis was performed in 102 tumors. Somatic KCNJ5 mutations (p.Gly151Arg or p.Leu168Arg) were found in 34% (129 of 380) of APA. They were significantly more prevalent in females (49%) than males (19%; P < 10(-3)) and in younger patients (42.1 +/- 1.0 versus 47.6 +/- 0.7 years; P < 10(-3)) and were associated with higher preoperative aldosterone levels (455 +/- 26 versus 376 +/- 17 ng/L; P = 0.012) but not with therapeutic outcome after surgery. Germline KCNJ5 mutations were found neither in patients with APA nor those with bilateral adrenal hyperplasia. Somatic KCNJ5 mutations were specific for APA, because they were not identified in 25 peritumoral adrenal tissues or 16 cortisol-producing adenomas. Hierarchical clustering of transcriptome profiles showed that APAs with p.Gly151Arg or p.Leu168Arg mutations were indistinguishable from tumors without KCNJ5 mutations. In conclusion, although a large proportion of sporadic APAs harbors somatic KCNJ5 mutations, germline mutations are not similarly causative for bilateral adrenal hyperplasia. KCNJ5 mutation carriers are more likely to be females; younger age and higher aldosterone levels at diagnosis suggest that KCNJ5 mutations may be associated with a more florid phenotype of primary aldosteronism. (Hypertension. 2012; 59: 592-598.). Online Data Supplement