{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:54:16Z","timestamp":1790816056847,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"<jats:p>Primary aldosteronism (PA) is a common cause of secondary hypertension. Recent technological advances in genetic analysis have provided a better understanding of the molecular pathogenesis of this disease. The application of next-generation sequencing has resulted in the identification of somatic mutations in aldosterone-producing adenoma (APA), a major subtype of PA. Based on the recent findings using a sequencing method that selectively targets the tumor region where aldosterone synthase (CYP11B2) is expressed, the vast majority of APAs appear to harbor a somatic mutation in one of the aldosterone-driver genes, including <jats:italic>KCNJ5<\/jats:italic>, <jats:italic>ATP1A1<\/jats:italic>, <jats:italic>ATP2B3<\/jats:italic>, <jats:italic>CACNA1D<\/jats:italic>, <jats:italic>CACNA1H<\/jats:italic>, and <jats:italic>CLCN2<\/jats:italic>. Mutations in these genes alter intracellular ion homeostasis and enhance aldosterone production. In a small subset of APAs, somatic activating mutations in the <jats:italic>CTNNB1<\/jats:italic> gene, which encodes \u03b2-catenin, have also been detected. Accumulating evidence suggests that race and sex impact the somatic mutation spectrum of APA. Specifically, somatic mutations in the <jats:italic>KCNJ5<\/jats:italic> gene, encoding an inwardly rectifying K<jats:sup>+<\/jats:sup> channel, are common in APAs from Asian populations as well as women regardless of race. Associations between APA histology, genotype, and patient clinical characteristics have also been proposed, suggesting a potential need to consider race and sex for the management of PA patients. Herein, we review recent findings regarding somatic mutations in APA and discuss potential roles of race and sex on the pathophysiology of APA as well as possible clinical implications.<\/jats:p>","DOI":"10.1530\/eje-21-0031","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T15:04:13Z","timestamp":1619449453000},"page":"R1-R11","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":51,"title":["GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas"],"prefix":"10.1093","volume":"185","author":[{"given":"Kazutaka","family":"Nanba","sequence":"first","affiliation":[{"name":"1Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"2Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Rainey","sequence":"additional","affiliation":[{"name":"1Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"3Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/1\/EJE-21-0031.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/1\/EJE-21-0031.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:16Z","timestamp":1676391376000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/1\/R1\/6654316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0031","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]}}}