Clinical Science and Services, Royal Veterinary College, London, United Kingdom (A.W., H.S.).
Clinical Pharmacology and Precision Medicine, Queen Mary University of London, United Kingdom (A.W., M.B.).
Hypertension. 2024 Dec;81(12):2489-2500. doi: 10.1161/HYPERTENSIONAHA.124.23501. Epub 2024 Oct 21.
Primary aldosteronism (PA) is a common cause of human hypertension. Somatic mutations in , , , and are found in at least 80% of aldosterone-producing adenomas, which cause unilateral PA in humans. Somatic mutations have been identified infrequently in 7 other genes; few of these were known to play a role in aldosterone secretion before the discovery of their mutations. Interrogating somatic mutations in the domestic cat, in which spontaneous PA is also known to occur, might improve the understanding of normal adrenal gland physiology and the pathophysiology of PA.
DNA and RNA extracted from tissue from 13 cats with unilateral aldosterone-secreting tumors, including 8 carcinomas and 5 adenomas, underwent whole genome sequencing, targeted Sanger sequencing, and RNA sequencing. Single-nucleotide substitution variants were filtered to select those with a predicted deleterious effect on protein function and a suspected role in aldosterone secretion.
Probable functional somatic single-nucleotide polymorphisms (n=8) were found in 3 adenomas and 2 carcinomas. Mutations with predicted significant effects were identified in 2 genes also mutated in human PA; and , and in a residue of analogous to a common mutation. In contrast to humans, expression was much greater than in both feline tumor and nontumor adrenal tissue. No mutations were identified in , , , or
Similar mutations were identified in cats to those found in humans. It is, therefore, likely that both species have shared underlying selection pressures for mutations that increase aldosterone secretion.
原醛症（PA）是人类高血压的常见病因。在至少 80%的产生醛固酮的腺瘤中发现了 、 、 和 的体细胞突变，这些突变导致人类单侧 PA。在发现其突变之前，在其他 7 个基因中很少发现体细胞突变；其中很少有人知道它们的突变在醛固酮分泌中起作用。在自发性 PA 也已知发生的家猫中检测体细胞突变，可能会提高对正常肾上腺生理学和 PA 病理生理学的理解。
从 13 只单侧醛固酮分泌肿瘤（包括 8 例癌和 5 例腺瘤）的组织中提取 DNA 和 RNA，进行全基因组测序、靶向 Sanger 测序和 RNA 测序。筛选单核苷酸取代变体，以选择对蛋白质功能具有预测有害影响并疑似与醛固酮分泌有关的变体。
在 3 个腺瘤和 2 个癌中发现了可能具有功能的体细胞单核苷酸多态性（n=8）。在 2 个在人类 PA 中也发生突变的基因中鉴定出具有预测显著影响的突变； 和 ，以及类似于常见 突变的残基。与人类不同的是， 在猫的肿瘤和非肿瘤肾上腺组织中的表达均远高于 。在 、 、 或 中未发现突变。
在猫中鉴定出与在人类中发现的相似的突变。因此，两种物种都可能具有增加醛固酮分泌的突变的共同选择压力。
