vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.443vavilov-1802Research ArticleМЕДИЦИНСКАЯ ГЕНЕТИКАMEDICAL GENETICSГенетика и патофизиология низкорениновой артериальной гипертонииGenetics and pathophysiology of low-renin arterial hypertensionhttps://orcid.org/0000-0002-1550-1647МаркельА. Л.MarkelA. L.markel@bionet.nsc.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics, SB RAS; Russia Novosibirsk State UniversityRussian Federation20180101201922810001008Copyright © Маркель А.Л., 20192019Маркель А.Л.Markel A.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1802

Обзор посвящен рассмотрению вопросов генетической детерминации и патофизиологии одной из форм гипертонической болезни – низкорениновой артериальной гипертонии. На первый взгляд, развитие низкорениновой гипертонии представляется «противоестественным», так как ренин как ключевой фермент ренин-ангиотензиновой системы, играющей важную роль в процессе формирования гипертонической болезни, при низкорениновой гипертонии подавлен. В то же время самые популярные лекарства, используемые при лечении гипертонической болезни, относятся к классу блокаторов ренин-ангиотензиновой системы. Разрешить противоречия позволили исследования генетики и патофизиологии некоторых групп больных с характерными, объединяющими этих больных симптомами. Генетические исследования последних десятилетий с использованием как семейного анализа, так и современных молекулярно-генетических технологий позволили выявить основные механизмы развития низкорениновой гипертонии, которые можно классифицировать в качестве определенных синдромов с вполне изученной патофизиологией их развития. К этим синдромам относятся случаи спорадически возникающих соматических мутаций в клетках коры надпочечников, которые начинают продуцировать повышенное количество альдостерона. Выявлено несколько наследственных олигогенных форм низкорениновых гипертензий, часть из которых также связана с гиперпродукцией альдостерона, другая же часть обусловливает развитие низкорениновой гипертонии за счет нарушений регуляции функции ионных каналов почки. Открытие форм артериальной гипертонии с известными механизмами имеет первостепенное значение для медицины, так как позволяет проводить целевую эффективную терапию и в ряде случаев достигать полного излечения. Тем не менее основной контингент больных с низкорениновой гипертонией принадлежит к группе больных с невыясненной до конца этиологией, так как их развитие связано с полигенными системами и со значительным влиянием средовых факторов. Исследование генетико-физиологических механизмов низкорениновых форм артериальной гипертонии дает показательный пример того, как проникновение в интимные механизмы регуляции артериального давления в каждом конкретном случае позволяет идентифицировать отдельные специфические синдромы и устанавливать исходные причины заболевания. Очевидно, на этом пути обеспечен прогресс в раскрытии причин и механизмов эссенциальной гипертонической болезни человека.

The review is devoted to the consideration of genetic determination and pathophysiology of one of the forms of hypertensive disease known as low-renin hypertension. At frst glance, the development of low-renin hypertension is “unnatural”, as renin, as a key enzyme of the renin-angiotensin system, which plays an important role in the development of hypertensive disease, is suppressed in low-renin hypertension. At the same time, the most important drugs actual in the treatment of hypertensive disease belong to the renin-angiotensin system blockers. This contradiction was resolved by a study of genetic and pathophysiological mechanisms of hypertension in some groups of patients with characteristic symptoms bringing these people together. Genetic studies of some recent decades using both family analysis and modern molecular genetic technologies have revealed the main mechanisms underlying low-renin hypertension, which can be classifed as certain syndromes with well-defned genetic and clinical features. These syndromes include cases of sporadically occurring somatic mutations in the cells of the adrenal cortex, which begin to produce aldosterone in increased amounts. Also, several oligogenic forms of low-renin hypertension were studied, some of which are associated with the hyperproduction of aldosterone, but in the others the development of low-renin hypertension was associated with mutations of genes involved in regulation of the functioning of the kidney ion channels. The discovery of some types of arterial hypertension with known mechanisms of their development is of paramount importance for medicine, as it allows for targeted efective therapy and in some cases for achieving a complete cure. However, the main contingent of patients with low-renin hypertension belongs to cases with unexplained etiology, as their development is associated with polygenic systems and with a signifcant influence of numerous environmental factors. The study of genetic and physiological mechanisms of various forms of low-renin arterial hypertension provides a good example of how penetration into the intimate mechanisms of the blood pressure regulation in each personal case makes it possible to identify some specifc syndromes and establish its fnal causes. It seems that progress in understanding the causes and mechanisms of essential hypertension lies along this way.

артериальное давлениерегуляциягипертоническая болезньнизкорениновая гипертониягенетическая детерминацияпатофизиологияальдостеронренинионные каналы почкиarterial blood pressureregulationhypertensive diseaselow-renin hypertensiongenetic determinationpathophysiologyaldosteronereninkidney ion channelsReferencesÅkerström T., Maharjan R., Willenberg H.S., Cupisti K., Ip J., Moser A., Stålberg P., Robinson B., Iwen K.A., Dralle H., Walz M.K., Lehnert H., Sidhu S., Gomez-Sanchez C., Hellman P., Björklund P. Activating mutations in CTNNB1 in aldosterone producing adenomas. Sci. Rep. 2016;6:19546. DOI 10.1161/01.HYP.8.2.93.Åkerström T., Maharjan R., Willenberg H.S., Cupisti K., Ip J., Moser A., Stålberg P., Robinson B., Iwen K.A., Dralle H., Walz M.K., Lehnert H., Sidhu S., Gomez-Sanchez C., Hellman P., Björklund P. Activating mutations in CTNNB1 in aldosterone producing adenomas. Sci. Rep. 2016;6:19546. DOI 10.1161/01.HYP.8.2.93.Antonov Y.V., Alexandrovich Y.V., Redina O.E., Gilinsky M.A., Markel A.L. Stress and hypertensive disease: adrenals as a link. Experimental study on hypertensive ISIAH rat strain. Clin. Exp. Hypertens. 2016;38(5):415-423. DOI 10.3109/10641963.2015.1116546.Antonov Y.V., Alexandrovich Y.V., Redina O.E., Gilinsky M.A., Markel A.L. Stress and hypertensive disease: adrenals as a link. Experimental study on hypertensive ISIAH rat strain. Clin. Exp. Hypertens. 2016;38(5):415-423. DOI 10.3109/10641963.2015.1116546.Azizan E.A.B., Poulsen H., Tuluc P., Zhou J., Clausen M.V., Lieb A., Maniero C., Garg S., Bochukova E.G., Zhao W., Shaikh L.H., Brighton C.A., Teo A.E.D., Davenport A.P., Dekkers T., Tops B., Küsters B., Ceral J., Yeo G.S.H., Neogi S.G., McFarlane I., Rosenfeld N., Marass F., Hadfeld J., Margas W., Chaggar K., Solar M., Deinum J., Dolphin A.C., Farooqi I.S., Striessnig J., Nissen P., Brown M.J. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat. Genet. 2013;45: 1055-1060. DOI 10.1038/ng.2716.Azizan E.A.B., Poulsen H., Tuluc P., Zhou J., Clausen M.V., Lieb A., Maniero C., Garg S., Bochukova E.G., Zhao W., Shaikh L.H., Brighton C.A., Teo A.E.D., Davenport A.P., Dekkers T., Tops B., Küsters B., Ceral J., Yeo G.S.H., Neogi S.G., McFarlane I., Rosenfeld N., Marass F., Hadfeld J., Margas W., Chaggar K., Solar M., Deinum J., Dolphin A.C., Farooqi I.S., Striessnig J., Nissen P., Brown M.J. Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat. Genet. 2013;45: 1055-1060. DOI 10.1038/ng.2716.Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Välimäki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M., Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R.P., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482:98-102. DOI 10.1038/nature10814.Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Välimäki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M., Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R.P., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature. 2012;482:98-102. DOI 10.1038/nature10814.Calhoun D.A. Aldosteronism and hypertension. Clin. J. Am. Soc. Nephrol. 2006;1:1039-1045. DOI 10.2215/CJN.01060306.Calhoun D.A. Aldosteronism and hypertension. Clin. J. Am. Soc. Nephrol. 2006;1:1039-1045. DOI 10.2215/CJN.01060306.Carvajal C.A., Tapia-Castillo A., Valdivia C.P., Allende F., Solari S., Lagos C.F., Campino C., Martinez-Aguayo A., Vecchiola A., Pinochet C., Godoy C., Iturrieta V., Baudrand R., Fardella C.E. Serum cortisol and cortisone as potential biomarkers of partial 11β-hydroxysteroid dehydrogenase type 2 defciency. Am. J. Hypertens. 2018;31(8):910-918. Downloaded from https://academic.oup.com/ajh/advance-article-abstract/DOI/10.1093/ajh/hpy051/4956699 by University of California, Santa Barbara user on 27 June 2018.Carvajal C.A., Tapia-Castillo A., Valdivia C.P., Allende F., Solari S., Lagos C.F., Campino C., Martinez-Aguayo A., Vecchiola A., Pinochet C., Godoy C., Iturrieta V., Baudrand R., Fardella C.E. Serum cortisol and cortisone as potential biomarkers of partial 11β-hydroxysteroid dehydrogenase type 2 defciency. Am. J. Hypertens. 2018;31(8):910-918. Downloaded from https://academic.oup.com/ajh/advance-article-abstract/DOI/10.1093/ajh/hpy051/4956699 by University of California, Santa Barbara user on 27 June 2018.Channick B.J., Adlin E.V., Marks A.D. Suppressed plasma renin activity in hypertension. Arch. Intern. Med. 1969;123:131-140. DOI 10.1001/archinte.1969.00300120019003.Channick B.J., Adlin E.V., Marks A.D. Suppressed plasma renin activity in hypertension. Arch. Intern. Med. 1969;123:131-140. DOI 10.1001/archinte.1969.00300120019003.Charles L., Triscott J., Dobbs B. Secondary hypertension: discovering the underlying cause. Am. Fam. Physician. 2017;96(7):453-461.Charles L., Triscott J., Dobbs B. Secondary hypertension: discovering the underlying cause. Am. Fam. Physician. 2017;96(7):453-461.Choi M., Scholl U.I., Yue P., Björklund P., Zhao B., Nelson-Williams C., Ji W., Cho Y., Patel A., Men C.J., Lolis E., Wisgerhof M.V., Geller D.S., Mane S., Hellman P., Westin G., Åkerström G., Wang W., Carling T., Lifton R.P. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011;331(6018):768-772. DOI 10.1126/science.1198785.Choi M., Scholl U.I., Yue P., Björklund P., Zhao B., Nelson-Williams C., Ji W., Cho Y., Patel A., Men C.J., Lolis E., Wisgerhof M.V., Geller D.S., Mane S., Hellman P., Westin G., Åkerström G., Wang W., Carling T., Lifton R.P. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011;331(6018):768-772. DOI 10.1126/science.1198785.Conn J.W. Evolution of primary aldosteronism as a highly specifc clinical entity. J. Am. Med. Assoc. 1960;172:1650-1653. DOI 10.1001/jama.1960.63020150008016.Conn J.W. Evolution of primary aldosteronism as a highly specifc clinical entity. J. Am. Med. Assoc. 1960;172:1650-1653. DOI 10.1001/jama.1960.63020150008016.Dahl L.K., Heine M., Tassinari L. Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature. 1962;194:480-482. DOI 10.1038/194480b0.Dahl L.K., Heine M., Tassinari L. Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature. 1962;194:480-482. DOI 10.1038/194480b0.Elijovich F., Weinberger M.H., Anderson C.A.M., Appel L.J., Bursztyn M., Cook N.R., Dart R.A., Newton-Cheh C.H., Sacks F.M., Laffer C.L. On behalf of the American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Genomic and Precision Medicine; and Stroke Council. Salt sensitivity of blood pressure: a scientifc statement from the American Heart Association. [published online ahead of print July 21, 2016]. Hypertension. DOI 10.1161/HYP.0000000000000047.Elijovich F., Weinberger M.H., Anderson C.A.M., Appel L.J., Bursztyn M., Cook N.R., Dart R.A., Newton-Cheh C.H., Sacks F.M., Laffer C.L. On behalf of the American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Genomic and Precision Medicine; and Stroke Council. Salt sensitivity of blood pressure: a scientifc statement from the American Heart Association. [published online ahead of print July 21, 2016]. Hypertension. DOI 10.1161/HYP.0000000000000047.Fernandes-Rosa F.L., Daniil G., Orozco I.J., Göppner C., El Zein R., Jain V., Boulkroun S., Jeunemaitre X., Amar L., Lefebvre H., Schwarzmayr T., Strom T.M., Jentsch T.J., Zennaro M.-C. A gainof-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat. Genet. 2018;50:355-361. DOI 10.1038/s41588-018-0053-8.Fernandes-Rosa F.L., Daniil G., Orozco I.J., Göppner C., El Zein R., Jain V., Boulkroun S., Jeunemaitre X., Amar L., Lefebvre H., Schwarzmayr T., Strom T.M., Jentsch T.J., Zennaro M.-C. A gainof-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat. Genet. 2018;50:355-361. DOI 10.1038/s41588-018-0053-8.Fernandes-Rosa F.L., Williams T.A., Riester A., Steichen O., Beuschlein F., Boulkroun S., Strom T.M., Monticone S., Amar L., Meatchi T., Mantero F., Cicala M.-V., Quinkler M., Fallo F., Allolio B., Bernini G., Maccario M., Giacchetti G., Jeunemaitre X., Mulatero P., Reincke M., Zennaro M.-C. Genetic spectrum and clinical correlates of somatic mutations in aldosterone¬producing adenoma. Hypertension. 2014;64:354-361. DOI 10.1161/HYPERTENSIONAHA.114.03419.Fernandes-Rosa F.L., Williams T.A., Riester A., Steichen O., Beuschlein F., Boulkroun S., Strom T.M., Monticone S., Amar L., Meatchi T., Mantero F., Cicala M.-V., Quinkler M., Fallo F., Allolio B., Bernini G., Maccario M., Giacchetti G., Jeunemaitre X., Mulatero P., Reincke M., Zennaro M.-C. Genetic spectrum and clinical correlates of somatic mutations in aldosterone¬producing adenoma. Hypertension. 2014;64:354-361. DOI 10.1161/HYPERTENSIONAHA.114.03419.Freel E.M., Connell J.M.C. Mechanisms of hypertension: the expanding role of aldosterone. J. Am. Soc. Nephrol. 2004;15(8):1993-2001. DOI 10.1097/01.ASN.0000132473.50966.14.Freel E.M., Connell J.M.C. Mechanisms of hypertension: the expanding role of aldosterone. J. Am. Soc. Nephrol. 2004;15(8):1993-2001. DOI 10.1097/01.ASN.0000132473.50966.14.Funder J.W., Carey R.M., Mantero F., Murad M.H., Reincke M., Shibata H., Stowasser M., Young W.F. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2016;101:1889-1916. DOI 10.1210/jc.2015-4061.Funder J.W., Carey R.M., Mantero F., Murad M.H., Reincke M., Shibata H., Stowasser M., Young W.F. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2016;101:1889-1916. DOI 10.1210/jc.2015-4061.Geller D.S., Farhi A., Pinkerton N., Fradley M., Moritz M., Spitzer A., Meinke G., Tsai F.T., Sigler P.B., Lifton R.P. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000;289:119-123. DOI 10.1126/science.289.5476.119.Geller D.S., Farhi A., Pinkerton N., Fradley M., Moritz M., Spitzer A., Meinke G., Tsai F.T., Sigler P.B., Lifton R.P. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000;289:119-123. DOI 10.1126/science.289.5476.119.Geller D.S., Zhang J., Wisgerhof M.V., Shackleton C., Kashgarian M., Lifton R.P. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J. Clin. Endocrinol. Metab. 2008;93:3117-3123. DOI 10.1210/jc.2008-0594.Geller D.S., Zhang J., Wisgerhof M.V., Shackleton C., Kashgarian M., Lifton R.P. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J. Clin. Endocrinol. Metab. 2008;93:3117-3123. DOI 10.1210/jc.2008-0594.Gianmichele G., O’Shaughenessy K., Murthy M. Role for germline mutations and a rare coding single nucleotide polymorphism within the KCNJ5 potassium channel in a large cohort of sporadic cases of primary aldosteronism. Hypertension. 2014;63:783-789. DOI 10.1016/j.clinthera.2014.05.058.Gianmichele G., O’Shaughenessy K., Murthy M. Role for germline mutations and a rare coding single nucleotide polymorphism within the KCNJ5 potassium channel in a large cohort of sporadic cases of primary aldosteronism. Hypertension. 2014;63:783-789. DOI 10.1016/j.clinthera.2014.05.058.Gordon R.D. Syndrome of hypertension and hyperkalemia with normal glomerular fltration rate. Hypertension. 1986;8(2):93-102. DOI 10.1161/01.HYP.8.2.93.Gordon R.D. Syndrome of hypertension and hyperkalemia with normal glomerular fltration rate. Hypertension. 1986;8(2):93-102. DOI 10.1161/01.HYP.8.2.93.Griffng G.T., Wilson T.E., Melby J.C. Alterations in aldosterone secretion and metabolism in low renin hypertension. J. Clin. Endocrinol. Metab. 1990;71:1454-1460. DOI 10.1210/jcem-71-6-1454.Griffng G.T., Wilson T.E., Melby J.C. Alterations in aldosterone secretion and metabolism in low renin hypertension. J. Clin. Endocrinol. Metab. 1990;71:1454-1460. DOI 10.1210/jcem-71-6-1454.Hanukoglu I., Hanukoglu A. Epithelial sodium channel (ENaC) family: phylogeny, structure-function, tissue distribution, and associated inherited diseases. Gene. 2016;579:95-132. DOI 10.1016/j.gene.2015.12.061.Hanukoglu I., Hanukoglu A. Epithelial sodium channel (ENaC) family: phylogeny, structure-function, tissue distribution, and associated inherited diseases. Gene. 2016;579:95-132. DOI 10.1016/j.gene.2015.12.061.Hypertension. Eds. E.L. Schiffrin, R.M. Touyz. London: Future Medicine, 2013.Hypertension. Eds. E.L. Schiffrin, R.M. Touyz. London: Future Medicine, 2013.Jacovic S., Zivkovic-Radojevic M., Petrovic D. Secondary hypertension: differential diagnosis and basic principles of treatment. Ser. J. Exp. Clin. Res. 2016;17(4):349-356. DOI 10.1515/SJECR_2015_0056.Jacovic S., Zivkovic-Radojevic M., Petrovic D. Secondary hypertension: differential diagnosis and basic principles of treatment. Ser. J. Exp. Clin. Res. 2016;17(4):349-356. DOI 10.1515/SJECR_2015_0056.Jose A., Crout J.R., Kaplan N.M. Suppressed plasma renin activity in essential hypertension. Roles of plasma volume, blood pressure, and sympathetic nervous system. Ann. Intern. Med. 1970;72:9-16. DOI 10.7326/0003-4819-72-1-9.Jose A., Crout J.R., Kaplan N.M. Suppressed plasma renin activity in essential hypertension. Roles of plasma volume, blood pressure, and sympathetic nervous system. Ann. Intern. Med. 1970;72:9-16. DOI 10.7326/0003-4819-72-1-9.Kaplan N.M. Hypokalemia in the hypertensive patient: with observations on the incidence of primary aldosteronism. Ann. Intern. Med. 1967;66:1079-1090. DOI 10.7326/0003-4819-66-6-1079.Kaplan N.M. Hypokalemia in the hypertensive patient: with observations on the incidence of primary aldosteronism. Ann. Intern. Med. 1967;66:1079-1090. DOI 10.7326/0003-4819-66-6-1079.Liddle G.W., Bledsoe T., Coppage W.S.J. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans. Assoc. Am. Phys. 1963;76:199-213. NII Article ID (NAID): 10018198924. http://ci.nii.ac.jp/naid/10018198924/Liddle G.W., Bledsoe T., Coppage W.S.J. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans. Assoc. Am. Phys. 1963;76:199-213. NII Article ID (NAID): 10018198924. http://ci.nii.ac.jp/naid/10018198924/Liu K., Qin F., Sun X., Zhang Y., Wang J., Wu Y., Ma W., Wang W., Wu X., Qin Y., Zhang H., Zhou X., Wu H., Hui R., Zou Y., Jiang X., Song L. Analysis of the genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients. J. Hypertens. 2018;36:502-509. DOI 10.1097/HJH.0000000000001556.Liu K., Qin F., Sun X., Zhang Y., Wang J., Wu Y., Ma W., Wang W., Wu X., Qin Y., Zhang H., Zhou X., Wu H., Hui R., Zou Y., Jiang X., Song L. Analysis of the genes involved in Mendelian forms of low-renin hypertension in Chinese early-onset hypertensive patients. J. Hypertens. 2018;36:502-509. DOI 10.1097/HJH.0000000000001556.Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B., Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfeld M., International Consortium for Blood Pressure (ICBP), Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.-J., Jeunemaitre X. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat. Genet. 2012;44:S1-S3. DOI 10.1038/ng.2218.Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B., Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfeld M., International Consortium for Blood Pressure (ICBP), Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.-J., Jeunemaitre X. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat. Genet. 2012;44:S1-S3. DOI 10.1038/ng.2218.MacConnachie A.A., Kelly K.F., McNamara A., Loughlin S., Gates L.J., Inglis G.C., Jamieson A., Connell J.M., Haites N.E. Rapid diagnosis and identifcation of cross-over sites in patients with glucocorticoid remediable aldosteronism. J. Clin. Endocrinol. Metab. 1998;83:4328-4331. DOI 10.1210/jcem.83.12.5309.MacConnachie A.A., Kelly K.F., McNamara A., Loughlin S., Gates L.J., Inglis G.C., Jamieson A., Connell J.M., Haites N.E. Rapid diagnosis and identifcation of cross-over sites in patients with glucocorticoid remediable aldosteronism. J. Clin. Endocrinol. Metab. 1998;83:4328-4331. DOI 10.1210/jcem.83.12.5309.Markou A., Sertedaki A., Kaltsas G., Androulakis I.I., Marakaki C., Pappa T., Gouli A., Papanastasiou L., Fountoulakis S., Zacharoulis A., Karavidas A., Ragkou D., Charmandari E., Chrousos G.P., Piaditis G.P. Stress-induced aldosterone hyper-secretion in a substantial subset of patients with essential hypertension. J. Clin. Endocrinol. Metab. 2015;100:2857-2864. DOI 10.1210/jc.2015-1268.Markou A., Sertedaki A., Kaltsas G., Androulakis I.I., Marakaki C., Pappa T., Gouli A., Papanastasiou L., Fountoulakis S., Zacharoulis A., Karavidas A., Ragkou D., Charmandari E., Chrousos G.P., Piaditis G.P. Stress-induced aldosterone hyper-secretion in a substantial subset of patients with essential hypertension. J. Clin. Endocrinol. Metab. 2015;100:2857-2864. DOI 10.1210/jc.2015-1268.Mishra S., Ingole S., Jain R. Salt sensitivity and its implication in clinical practice. Indian Heart J. 2018:70(4):556-564. DOI 10.1016/j.ihj.2017.10.006.Mishra S., Ingole S., Jain R. Salt sensitivity and its implication in clinical practice. Indian Heart J. 2018:70(4):556-564. DOI 10.1016/j.ihj.2017.10.006.Monticone S., Burrello J., Tizzani D., Bertello C., Viola A., Buffolo F., Gabetti L., Mengozzi G., Williams T.A., Rabbia F., Veglio F., Mulatero P. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J. Am. Coll. Cardiol. 2017a;69(14):1812-1820. DOI 10.1016/j.jacc.2017.01.052.Monticone S., Burrello J., Tizzani D., Bertello C., Viola A., Buffolo F., Gabetti L., Mengozzi G., Williams T.A., Rabbia F., Veglio F., Mulatero P. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J. Am. Coll. Cardiol. 2017a;69(14):1812-1820. DOI 10.1016/j.jacc.2017.01.052.Monticone S., D’Ascenzo F., Moretti C., Williams T.A., Veglio F., Gaita F., Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta¬analysis. Lancet Diabetes Endocrinol. 2018a;6:41-50. DOI 10.1016/S2213-8587(17)30319-4.Monticone S., D’Ascenzo F., Moretti C., Williams T.A., Veglio F., Gaita F., Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta¬analysis. Lancet Diabetes Endocrinol. 2018a;6:41-50. DOI 10.1016/S2213-8587(17)30319-4.Monticone S., Else T., Mulatero P., Williams T.A., Rainey W.E. Understanding primary aldosteronism: impact of next generation sequencing and expression profling. Mol. Cell Endocrinol. 2015a;399:311- 320. DOI 10.1016/j.mce.2014.09.015.Monticone S., Else T., Mulatero P., Williams T.A., Rainey W.E. Understanding primary aldosteronism: impact of next generation sequencing and expression profling. Mol. Cell Endocrinol. 2015a;399:311- 320. DOI 10.1016/j.mce.2014.09.015.Monticone S., Losano I., Tetti M., Buffolo F., Veglio F., Mulatero P. Diagnostic approach to low-renin hypertension. Clin. Endocrinol. 2018b;1-12. DOI 10.1111/cen.13741.Monticone S., Losano I., Tetti M., Buffolo F., Veglio F., Mulatero P. Diagnostic approach to low-renin hypertension. Clin. Endocrinol. 2018b;1-12. DOI 10.1111/cen.13741.Monticone S., Tetti M., Burrello J., Buffolo F., De Giovanni R., Veglio F., Williams T.A., Mulatero P. Familial hyperaldosteronism type III. J. Hum. Hypertens. 2017b;31:776-781. DOI 10.1038/jhh.2017.34.Monticone S., Tetti M., Burrello J., Buffolo F., De Giovanni R., Veglio F., Williams T.A., Mulatero P. Familial hyperaldosteronism type III. J. Hum. Hypertens. 2017b;31:776-781. DOI 10.1038/jhh.2017.34.Monticone S., Viola A., Rossato D., Veglio F., Reincke M., GomezSanchez C., Mulatero P. Adrenal vein sampling in primary aldoste- ronism: towards a standardised protocol. Lancet Diabetes Endocrinol. 2015b;3:296-303. DOI 10.1016/S2213-8587(14)70069-5.Monticone S., Viola A., Rossato D., Veglio F., Reincke M., GomezSanchez C., Mulatero P. Adrenal vein sampling in primary aldoste- ronism: towards a standardised protocol. Lancet Diabetes Endocrinol. 2015b;3:296-303. DOI 10.1016/S2213-8587(14)70069-5.Mulatero P., Milan A., Fallo F., Regolisti G., Pizzolo F., Fardella C., Mosso L., Marafetti L., Veglio F., Maccario M. Comparison of confrmatory tests for the diagnosis of primary aldosteronism. J. Clin. Endocrinol. Metab. 2006;91:2618-2623. DOI 10.1210/jc.2006-0078.Mulatero P., Milan A., Fallo F., Regolisti G., Pizzolo F., Fardella C., Mosso L., Marafetti L., Veglio F., Maccario M. Comparison of confrmatory tests for the diagnosis of primary aldosteronism. J. Clin. Endocrinol. Metab. 2006;91:2618-2623. DOI 10.1210/jc.2006-0078.Mulatero P., Monticone S., Bertello C., Viola A., Tizzani D., Iannaccone A., Crudo V., Burrello J., Milan A., Rabbia F., Veglio F. Longterm cardio¬ and cerebrovascular events in patients with primary aldosteronism. J. Clin. Endocrinol. Metab. 2013;98:4826-4833. DOI 10.1210/jc.2013-2805.Mulatero P., Monticone S., Bertello C., Viola A., Tizzani D., Iannaccone A., Crudo V., Burrello J., Milan A., Rabbia F., Veglio F. Longterm cardio¬ and cerebrovascular events in patients with primary aldosteronism. J. Clin. Endocrinol. Metab. 2013;98:4826-4833. DOI 10.1210/jc.2013-2805.Mulatero P., Rabbia F., Milan A., Paglieri C., Morello F., Chiandussi L., Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002;40:897-902. DOI 10.1016/S0895-7061(03)00766-0.Mulatero P., Rabbia F., Milan A., Paglieri C., Morello F., Chiandussi L., Veglio F. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism. Hypertension. 2002;40:897-902. DOI 10.1016/S0895-7061(03)00766-0.Mulatero P., Verhovez A., Morello F., Veglio F. Diagnosis and treatment of low-renin hypertension. Clin. Endocrinol. (Oxf). 2007;67:324- 334. DOI 10.1111/j.1365-2265.2007.02898.x.Mulatero P., Verhovez A., Morello F., Veglio F. Diagnosis and treatment of low-renin hypertension. Clin. Endocrinol. (Oxf). 2007;67:324- 334. DOI 10.1111/j.1365-2265.2007.02898.x.New M.I., Geller D.S., Fallo F., Wilson R.C. Monogenic low renin hypertension. Trends Endocrinol. Metab. 2005;16:92-97. DOI 10.1016/j.tem.2005.02.011.New M.I., Geller D.S., Fallo F., Wilson R.C. Monogenic low renin hypertension. Trends Endocrinol. Metab. 2005;16:92-97. DOI 10.1016/j.tem.2005.02.011.Rafestin-Oblin M.E., Souque A., Bocchi B., Pinon G., Fagart J., Vandewalle A. The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related. Endocrinology. 2003;144:528-533. DOI 10.1210/en.2002-220708.Rafestin-Oblin M.E., Souque A., Bocchi B., Pinon G., Fagart J., Vandewalle A. The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related. Endocrinology. 2003;144:528-533. DOI 10.1210/en.2002-220708.Rapp J.P., Dene H. Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 1985;7(1): 340-349.Rapp J.P., Dene H. Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 1985;7(1): 340-349.Sagnella G.A. Why is plasma renin activity lower in populations of African origin? J. Hum. Hypertens. 2001;15:17-25.Sagnella G.A. Why is plasma renin activity lower in populations of African origin? J. Hum. Hypertens. 2001;15:17-25.Salti I.S., Stiefel M., Ruse J.L., Laidlaw J.C. Non-tumorous “primary” aldosteronism. I. Type relieved by glucocorticoid (glucocorticoidremediable aldosteronism. Can. Med. Assoc. J. 1969;101:1-10.Salti I.S., Stiefel M., Ruse J.L., Laidlaw J.C. Non-tumorous “primary” aldosteronism. I. Type relieved by glucocorticoid (glucocorticoidremediable aldosteronism. Can. Med. Assoc. J. 1969;101:1-10.Scholl U.I., Goh G., Stölting G., de Oliveira R.C., Choi M., Overton J.D., Fonseca A.L., Korah R., Starker L.F., Kunstman J.W., Prasad M.L., Hartung E.A., Mauras N., Benson M.R., Brady T., Shapiro J.R., Loring E., Nelson-Williams C., Libutti S.K., Mane S., Hellman P., Westin G., Åkerström G., Björklund P., Carling T., Fahlke C., Hidalgo P., Lifton R.P. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat. Genet. 2013;45:1050-1054. DOI 10.1038/ng.2695.Scholl U.I., Goh G., Stölting G., de Oliveira R.C., Choi M., Overton J.D., Fonseca A.L., Korah R., Starker L.F., Kunstman J.W., Prasad M.L., Hartung E.A., Mauras N., Benson M.R., Brady T., Shapiro J.R., Loring E., Nelson-Williams C., Libutti S.K., Mane S., Hellman P., Westin G., Åkerström G., Björklund P., Carling T., Fahlke C., Hidalgo P., Lifton R.P. Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat. Genet. 2013;45:1050-1054. DOI 10.1038/ng.2695.Scholl U.I., Healy J.M., Thiel A., Fonseca A.L., Brown T.C., Kunstman J.W., Horne M.J., Dietrich D., Riemer J., Kücükköylü S., Reimer E.N., Reis A.C., Goh G., Kristiansen G., Mahajan A., Korah R., Lifton R.P., Prasad M.L., Carling T. Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype. Clin. Endocrinol. 2015a;83:779-789. DOI 10.1111/cen.12873. Epub 2015 Sep 23.Scholl U.I., Healy J.M., Thiel A., Fonseca A.L., Brown T.C., Kunstman J.W., Horne M.J., Dietrich D., Riemer J., Kücükköylü S., Reimer E.N., Reis A.C., Goh G., Kristiansen G., Mahajan A., Korah R., Lifton R.P., Prasad M.L., Carling T. Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype. Clin. Endocrinol. 2015a;83:779-789. DOI 10.1111/cen.12873. Epub 2015 Sep 23.Scholl U.I., Stölting G., Nelson-Williams C., Vichot A.A., Choi M., Loring E., Prasad M.L., Goh G., Carling T., Juhlin C.C., Quack I., Rump L.C., Thiel A., Lande M., Frazier B.G., Rasoulpour M., Bowlin D.L., Sethna C.B., Trachtman H., Fahlke C., Lifton R.P. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife. 2015b;4:e06315. DOI 10.7554/eLife.06315.Scholl U.I., Stölting G., Nelson-Williams C., Vichot A.A., Choi M., Loring E., Prasad M.L., Goh G., Carling T., Juhlin C.C., Quack I., Rump L.C., Thiel A., Lande M., Frazier B.G., Rasoulpour M., Bowlin D.L., Sethna C.B., Trachtman H., Fahlke C., Lifton R.P. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife. 2015b;4:e06315. DOI 10.7554/eLife.06315.Scholl U.I., Stölting G., Schewe J., Thiel A., Tan H., Nelson-Williams C., Vichot A.A., Jin S.C., Loring E., Untiet V. , Yoo T., Choi J., Xu S., Wu A., Kirchner M., Mertins P., Rump L.C., Onder A.M., Gamble C., McKenney D., Lash R.W., Jones D.P., Chune G., Gagliardi P., Choi M., Gordon R., Stowasser M., Fahlke C., Lifton R.P. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat. Genet. 2018;50(3):349-354. DOI 10.1038/s41588-018-0048-5.Scholl U.I., Stölting G., Schewe J., Thiel A., Tan H., Nelson-Williams C., Vichot A.A., Jin S.C., Loring E., Untiet V. , Yoo T., Choi J., Xu S., Wu A., Kirchner M., Mertins P., Rump L.C., Onder A.M., Gamble C., McKenney D., Lash R.W., Jones D.P., Chune G., Gagliardi P., Choi M., Gordon R., Stowasser M., Fahlke C., Lifton R.P. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat. Genet. 2018;50(3):349-354. DOI 10.1038/s41588-018-0048-5.Song Y., Yang S., He W., Hu J., Cheng Q., Wang Y., Luo T., Ma L., Zhen Q., Zhang S., Mei M., Wang Z., Qing H., Bruemmer D., Peng B., Li Q. Chongqing Primary Aldosteronism Study (CONPASS) Group. Confrmatory tests for the diagnosis of primary aldosteronism: a prospective diagnostic accuracy study. Hypertension. 2018;71(1):118- 124. DOI 10.1161/HYPERTENSIONAHA.117.10197.Song Y., Yang S., He W., Hu J., Cheng Q., Wang Y., Luo T., Ma L., Zhen Q., Zhang S., Mei M., Wang Z., Qing H., Bruemmer D., Peng B., Li Q. Chongqing Primary Aldosteronism Study (CONPASS) Group. Confrmatory tests for the diagnosis of primary aldosteronism: a prospective diagnostic accuracy study. Hypertension. 2018;71(1):118- 124. DOI 10.1161/HYPERTENSIONAHA.117.10197.Sutherland D.J., Ruse J.L., Laidlaw J.C. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can. Med. Assoc. J. 1966;95:1109-1119.Sutherland D.J., Ruse J.L., Laidlaw J.C. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can. Med. Assoc. J. 1966;95:1109-1119.Tetti M., Monticone S., Burrello J., Matarazzo P., Veglio F., Pasini B., Jeunemaitre X., Mulatero P. Liddle syndrome: review of the literature and description of a new case. Int. J. Mol. Sci. 2018;19(3):E812. DOI 10.3390/ijms19030812.Tetti M., Monticone S., Burrello J., Matarazzo P., Veglio F., Pasini B., Jeunemaitre X., Mulatero P. Liddle syndrome: review of the literature and description of a new case. Int. J. Mol. Sci. 2018;19(3):E812. DOI 10.3390/ijms19030812.Vilela L.A.P., Almeida M.Q. Diagnosis and management of primary aldosteronism. Arch. Endocrinol. Metab. 2017;61(3):305-312. DOI 10.1590/2359-3997000000274.Vilela L.A.P., Almeida M.Q. Diagnosis and management of primary aldosteronism. Arch. Endocrinol. Metab. 2017;61(3):305-312. DOI 10.1590/2359-3997000000274.Wang J.J., Peng K.Y., Wu V.C., Tseng F.Y., Wu K.D. CTNNB1 mutation in aldosterone producing adenoma. Endocrinol. Metab. (Seoul). 2017;32:332¬338. DOI 10.3803/EnM.2017.32.3.332.Wang J.J., Peng K.Y., Wu V.C., Tseng F.Y., Wu K.D. CTNNB1 mutation in aldosterone producing adenoma. Endocrinol. Metab. (Seoul). 2017;32:332¬338. DOI 10.3803/EnM.2017.32.3.332.Wang L.P., Yang K.Q., Jiang X.J., Wu H.Y., Zhang H.M., Zou Y.B., Song L., Bian J., Hui R.T., Liu Y.X., Zhou X.L. Prevalence of Liddle syndrome among young hypertension patients of undetermined cause in a chinese population. J. Clin. Hypertens. (Greenwich). 2015;17:902-907. DOI 10.1111/jch.12598.Wang L.P., Yang K.Q., Jiang X.J., Wu H.Y., Zhang H.M., Zou Y.B., Song L., Bian J., Hui R.T., Liu Y.X., Zhou X.L. Prevalence of Liddle syndrome among young hypertension patients of undetermined cause in a chinese population. J. Clin. Hypertens. (Greenwich). 2015;17:902-907. DOI 10.1111/jch.12598.Weinberger M.H. Salt sensitivity of blood pressure in humans. Hypertension. 1996;27:481-490.Weinberger M.H. Salt sensitivity of blood pressure in humans. Hypertension. 1996;27:481-490.Williams T.A., Lenders J.W.M., Mulatero P., Burrello J., Rottenkolber M., Adolf C., Satoh F., Amar L., Quinkler M., Deinum J., Beuschlein F., Kitamoto K.K., Pham U., Morimoto R., Umakoshi H., Prejbisz A., Kocjan T., Naruse M., Stowasser M., Nishikawa T., Young W.F. Jr, Gomez-Sanchez C.E., Funder J.W., Reincke M.; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5(9):689-699. DOI 10.1016/S2213-8587(17)30135-3.Williams T.A., Lenders J.W.M., Mulatero P., Burrello J., Rottenkolber M., Adolf C., Satoh F., Amar L., Quinkler M., Deinum J., Beuschlein F., Kitamoto K.K., Pham U., Morimoto R., Umakoshi H., Prejbisz A., Kocjan T., Naruse M., Stowasser M., Nishikawa T., Young W.F. Jr, Gomez-Sanchez C.E., Funder J.W., Reincke M.; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5(9):689-699. DOI 10.1016/S2213-8587(17)30135-3.Wilson F.H., Disse-Nicodème S., Choate K., Ishikawa K., NelsonWilliams C., Desitter I., Gunel M., Milford D.V., Lipkin G.W., Achard J.M., Feely M.P., Dussol B., Berland Y., Unwin R.J., Mayan H., Simon D.B., Farfel Z., Jeunemaitre X., Lifton R.P. Human hypertension caused by mutations in WNK kinases. Science. 2001;293(5532):1107-1112. DOI 10.1126/science.1062844.Wilson F.H., Disse-Nicodème S., Choate K., Ishikawa K., NelsonWilliams C., Desitter I., Gunel M., Milford D.V., Lipkin G.W., Achard J.M., Feely M.P., Dussol B., Berland Y., Unwin R.J., Mayan H., Simon D.B., Farfel Z., Jeunemaitre X., Lifton R.P. Human hypertension caused by mutations in WNK kinases. Science. 2001;293(5532):1107-1112. DOI 10.1126/science.1062844.Wilson R.C., Dave-Sharma S., Wei J.Q., Obeyesekere V.R., Li K., Ferrari P., Krozowski Z.S., Shackleton C.H.L., Bradlow L., Wiens T., New M.I. A genetic defect resulting in mild low-renin hypertension. Proc. Natl. Acad. Sci. USA. 1998;95:10200-10205.Wilson R.C., Dave-Sharma S., Wei J.Q., Obeyesekere V.R., Li K., Ferrari P., Krozowski Z.S., Shackleton C.H.L., Bradlow L., Wiens T., New M.I. A genetic defect resulting in mild low-renin hypertension. Proc. Natl. Acad. Sci. USA. 1998;95:10200-10205.Yagil C., Katni G., Rubattu S., Stolpe C., Kreutz R., Lindpaintner K., Ganten D., Ben-Ishay D., Yagil Y. Development, genotype and phenotype of a new colony of the Sabra hypertension prone (SBH/y) and resistant (SBN/y) rat model of salt sensitivity and resistance. J. Hypertens. 1996;14:1175-1182.Yagil C., Katni G., Rubattu S., Stolpe C., Kreutz R., Lindpaintner K., Ganten D., Ben-Ishay D., Yagil Y. Development, genotype and phenotype of a new colony of the Sabra hypertension prone (SBH/y) and resistant (SBN/y) rat model of salt sensitivity and resistance. J. Hypertens. 1996;14:1175-1182.Yau M., Haider S., Khattab A., Ling C., Mathew M., Zaidi S., Bloch M., Patel M., Ewert S., Abdullah W., Toygar A., Mudryi V., Al Badi M., Alzubdi M., Wilson R.C., Al Azkawi H.S., Ozdemir H.N., AbuAmer W., Hertecant J., Razzaghy-Azar M., Funder J.W., Al Senani A., Sun L., Kim S.-M., Yuen T., Zaidi M., New M.I. Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 defciency. Proc. Natl. Acad. Sci. USA. 2017;114:E11248-E11256. DOI 10.1073/pnas.1716621115.Yau M., Haider S., Khattab A., Ling C., Mathew M., Zaidi S., Bloch M., Patel M., Ewert S., Abdullah W., Toygar A., Mudryi V., Al Badi M., Alzubdi M., Wilson R.C., Al Azkawi H.S., Ozdemir H.N., AbuAmer W., Hertecant J., Razzaghy-Azar M., Funder J.W., Al Senani A., Sun L., Kim S.-M., Yuen T., Zaidi M., New M.I. Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 defciency. Proc. Natl. Acad. Sci. USA. 2017;114:E11248-E11256. DOI 10.1073/pnas.1716621115.

The authors declare that there are no conflicts of interest present.