{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:26:56Z","timestamp":1789475216024,"version":"build-2803163510"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:00:00Z","timestamp":1340841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:00:00Z","timestamp":1340841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hum Hypertens"],"published-print":{"date-parts":[[2013,4]]},"DOI":"10.1038\/jhh.2012.24","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T09:24:50Z","timestamp":1340875490000},"page":"237-244","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic variation in the renin\u2013angiotensin\u2013aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease"],"prefix":"10.1038","volume":"27","author":[{"given":"K L","family":"Ellis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B R","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Frampton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R W","family":"Troughton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R N","family":"Doughty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G A","family":"Whalley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C J","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A P","family":"Pilbrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Skelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T G","family":"Yandle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V A","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,6,28]]},"reference":[{"key":"BFjhh201224_CR1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1046\/j.1440-6047.2001.00230.x","volume":"10","author":"GL Khor","year":"2001","unstructured":"Khor GL . Cardiovascular epidemiology in the Asia-Pacific region. Asia Pac J Clin Nutr 2001; 10: 76\u201380.","journal-title":"Asia Pac J Clin Nutr"},{"key":"BFjhh201224_CR2","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1515\/REVEH.2008.23.3.167","volume":"23","author":"TE O'Toole","year":"2008","unstructured":"O'Toole TE, Conklin DJ, Bhatnagar A . Environmental risk factors for heart disease. Rev Environ Health 2008; 23: 167\u2013202.","journal-title":"Rev Environ Health"},{"key":"BFjhh201224_CR3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1517\/14796678.1.1.17","volume":"1","author":"F Cambien","year":"2005","unstructured":"Cambien F . Genetics and coronary heart disease. Future Cardiol 2005; 1: 17\u201327.","journal-title":"Future Cardiol"},{"key":"BFjhh201224_CR4","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nature05911","volume":"447","author":"Wellcome Trust Case Control Consortium","year":"2007","unstructured":"Wellcome Trust Case Control Consortium Genome-wide association study of 14\u2009000 cases of seven common diseases and 3000 shared controls. Nature 2007; 447: 661\u2013678.","journal-title":"Nature"},{"key":"BFjhh201224_CR5","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/j.biocel.2005.01.012","volume":"37","author":"M Kurdi","year":"2005","unstructured":"Kurdi M, De Mello WC, Booz GW . Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components. Int J Biochem Cell Biol 2005; 37: 1357\u20131367.","journal-title":"Int J Biochem Cell Biol"},{"key":"BFjhh201224_CR6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.18553\/jmcp.2007.13.s8-b.9","volume":"13","author":"SA Atlas","year":"2007","unstructured":"Atlas SA . The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm 2007; 13: 9\u201320.","journal-title":"J Manag Care Pharm"},{"key":"BFjhh201224_CR7","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1210\/en.2003-0150","volume":"144","author":"JL Lavoie","year":"2003","unstructured":"Lavoie JL, Sigmund CD . Minireview: overview of the renin-angiotensin system--an endocrine and paracrine system. Endocrinology 2003; 144: 2179\u20132183.","journal-title":"Endocrinology"},{"key":"BFjhh201224_CR8","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1056\/NEJMra000050","volume":"345","author":"KT Weber","year":"2001","unstructured":"Weber KT . Aldosterone in congestive heart failure. N Engl J Med 2001; 345: 1689\u20131697.","journal-title":"N Engl J Med"},{"key":"BFjhh201224_CR9","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1056\/NEJM199412013312227","volume":"331","author":"PC White","year":"1994","unstructured":"White PC . Disorders of aldosterone biosynthesis and action. N Engl J Med 1994; 331: 250\u2013248.","journal-title":"N Engl J Med"},{"key":"BFjhh201224_CR10","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1161\/01.CIR.99.17.2255","volume":"99","author":"H Schunkert","year":"1999","unstructured":"Schunkert H, Hengstenberg C, Holmer SR, Broeckel U, Luchner A, Muscholl MW et al. Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. Circulation 1999; 99: 2255\u20132260.","journal-title":"Circulation"},{"key":"BFjhh201224_CR11","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199909023411001","volume":"341","author":"B Pitt","year":"1999","unstructured":"Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med 1999; 341: 709\u2013717.","journal-title":"N Engl J Med"},{"key":"BFjhh201224_CR12","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s00109-008-0344-0","volume":"86","author":"X Jeunemaitre","year":"2008","unstructured":"Jeunemaitre X . Genetics of the human renin angiotensin system. J Mol Med 2008; 86: 637\u2013641.","journal-title":"J Mol Med"},{"key":"BFjhh201224_CR13","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1210\/jcem-63-1-72","volume":"63","author":"TG Yandle","year":"1986","unstructured":"Yandle TG, Espiner EA, Nicholls MG, Duff H . Radioimmunoassay and characterization of atrial natriuretic peptide in human plasma. J Clin Endocrinol Metab 1986; 63: 72\u201379.","journal-title":"J Clin Endocrinol Metab"},{"key":"BFjhh201224_CR14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1006\/bbrc.1999.0225","volume":"255","author":"T Seidler","year":"1999","unstructured":"Seidler T, Pemberton C, Yandle T, Espiner E, Nicholls G, Richards M . The amino terminal regions of proBNP and proANP oligomerise through leucine zipper-like coiled-coil motifs. Biochem Biophys Res Commun 1999; 255: 495\u2013501.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFjhh201224_CR15","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1097\/00005344-199801000-00017","volume":"31","author":"MT Rademaker","year":"1998","unstructured":"Rademaker MT, Charles CJ, Espiner EA, Nicholls MG, Richards AM, Kosoglou T . Combined neutral endopeptidase and angiotensin-converting enzyme inhibition in heart failure: role of natriuretic peptides and angiotensin II. J Cardiovasc Pharmacol 1998; 31: 116\u2013125.","journal-title":"J Cardiovasc Pharmacol"},{"key":"BFjhh201224_CR16","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1046\/j.1365-2265.1997.2361058.x","volume":"47","author":"PJ Hunt","year":"1997","unstructured":"Hunt PJ, Richards AM, Nicholls MG, Yandle TG, Doughty RN, Espiner EA . Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP): a new marker of cardiac impairment. Clin Endocrinol 1997; 47: 287\u2013296.","journal-title":"Clin Endocrinol"},{"key":"BFjhh201224_CR17","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/0196-9781(93)90102-M","volume":"14","author":"TG Yandle","year":"1993","unstructured":"Yandle TG, Fisher S, Charles C, Espiner EA, Richards AM . The ovine hypothalamus and pituitary have markedly different distribution of C-type natriuretic peptide forms. Peptides 1993; 14: 713\u2013716.","journal-title":"Peptides"},{"key":"BFjhh201224_CR18","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/S0021-9258(19)45622-6","volume":"247","author":"AL Steiner","year":"1972","unstructured":"Steiner AL, Pagliara AS, Chase LR, Kipnis DM . Radioimmunoassay for cyclic nucleotides. II. Adenosine 3\u2032,5\u2032-monophosphate and guanosine 3\u2032,5\u2032-monophosphate in mammalian tissues and body fluids. J Biol Chem 1972; 247: 1114\u20131120.","journal-title":"J Biol Chem"},{"key":"BFjhh201224_CR19","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S0894-7317(89)80014-8","volume":"2","author":"NB Schiller","year":"1989","unstructured":"Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989; 2: 358\u2013367.","journal-title":"J Am Soc Echocardiogr"},{"key":"BFjhh201224_CR20","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0735-1097(02)02927-3","volume":"41","author":"BR Palmer","year":"2003","unstructured":"Palmer BR, Pilbrow AP, Yandle TG, Frampton CM, Richards AM, Nicholls MG et al. Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction. J Am Coll Cardiol 2003; 41: 729\u2013736.","journal-title":"J Am Coll Cardiol"},{"issue":"Suppl 1","key":"BFjhh201224_CR21","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1186\/1471-2350-8-S1-S3","volume":"8","author":"D Levy","year":"2007","unstructured":"Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ et al. Framingham Heart Study 100\u2009K Project: genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet 2007; 8 (Suppl 1): S3.","journal-title":"BMC Med Genet"},{"key":"BFjhh201224_CR22","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1161\/01.HYP.0000253061.30170.68","volume":"49","author":"AP Pilbrow","year":"2007","unstructured":"Pilbrow AP, Palmer BR, Frampton CM, Yandle TG, Troughton RW, Campbell E et al. Angiotensinogen M235T and T174M gene polymorphisms in combination doubles the risk of mortality in heart failure. Hypertension 2007; 49: 322\u2013327.","journal-title":"Hypertension"},{"key":"BFjhh201224_CR23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0092-8674(92)90275-H","volume":"71","author":"X Jeunemaitre","year":"1992","unstructured":"Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A et al. Molecular basis of human hypertension: role of angiotensinogen. Cell 1992; 71: 169\u2013180.","journal-title":"Cell"},{"key":"BFjhh201224_CR24","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1172\/JCI119343","volume":"99","author":"I Inoue","year":"1997","unstructured":"Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M et al. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997; 99: 1786\u20131797.","journal-title":"J Clin Invest"},{"key":"BFjhh201224_CR25","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1210\/jcem-67-6-1134","volume":"67","author":"AM Richards","year":"1988","unstructured":"Richards AM, McDonald D, Fitzpatrick MA, Nicholls MG, Espiner EA, Ikram H et al. Atrial natriuretic hormone has biological effects in man at physiological plasma concentrations. J Clin Endocrinol Metab 1988; 67: 1134\u20131139.","journal-title":"J Clin Endocrinol Metab"},{"key":"BFjhh201224_CR26","doi-asserted-by":"publisher","first-page":"787","DOI":"10.2147\/VHRM.S1905","volume":"4","author":"A Ribeiro-Oliveira","year":"2008","unstructured":"Ribeiro-Oliveira A, Nogueira AI, Pereira RM, Boas WW, Dos Santos RA . Simoes e Silva AC. The renin-angiotensin system and diabetes: an update. Vasc Health Risk Manag 2008; 4: 787\u2013803.","journal-title":"Vasc Health Risk Manag"},{"key":"BFjhh201224_CR27","first-page":"197","volume":"51","author":"L Tiret","year":"1992","unstructured":"Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1992; 51: 197\u2013205.","journal-title":"Am J Hum Genet"},{"key":"BFjhh201224_CR28","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1161\/01.CIR.101.17.2060","volume":"101","author":"J Higaki","year":"2000","unstructured":"Higaki J, Baba S, Katsuya T, Sato N, Ishikawa K, Mannami T et al. Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the Suita Study. Circulation 2000; 101: 2060\u20132065.","journal-title":"Circulation"},{"key":"BFjhh201224_CR29","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/359641a0","volume":"359","author":"F Cambien","year":"1992","unstructured":"Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641\u2013644.","journal-title":"Nature"},{"key":"BFjhh201224_CR30","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S1388-9842(00)00070-2","volume":"2","author":"GK Davis","year":"2000","unstructured":"Davis GK, Millner RW, Roberts DH . Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion\/deletion polymorphism and left ventricular function. Eur J Heart Fail 2000; 2: 253\u2013256.","journal-title":"Eur J Heart Fail"},{"key":"BFjhh201224_CR31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1161\/01.HYP.24.1.63","volume":"24","author":"A Bonnardeaux","year":"1994","unstructured":"Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24: 63\u201369.","journal-title":"Hypertension"},{"key":"BFjhh201224_CR32","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1161\/01.HYP.28.6.1076","volume":"28","author":"M Castellano","year":"1996","unstructured":"Castellano M, Muiesan ML, Beschi M, Rizzoni D, Cinelli A, Salvetti M et al. Angiotensin II type 1 receptor A\/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure. Hypertension 1996; 28: 1076\u20131080.","journal-title":"Hypertension"},{"key":"BFjhh201224_CR33","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1086\/519979","volume":"81","author":"P Sethupathy","year":"2007","unstructured":"Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS et al. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet 2007; 81: 405\u2013413.","journal-title":"Am J Hum Genet"},{"key":"BFjhh201224_CR34","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.amjhyper.2007.04.023","volume":"20","author":"TD Smilde","year":"2007","unstructured":"Smilde TD, Zuurman MW, Hillege HL, van Veldhuisen DJ, van Gilst WH, van der Steege G et al. Renal function dependent association of AGTR1 polymorphism (A1166C) and electrocardiographic left-ventricular hypertrophy. Am J Hypertens 2007; 20: 1097\u20131103.","journal-title":"Am J Hypertens"},{"key":"BFjhh201224_CR35","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1677\/jme.0.0280125","volume":"28","author":"MH Bassett","year":"2002","unstructured":"Bassett MH, Zhang Y, Clyne C, White PC, Rainey WE . Differential regulation of aldosterone synthase and 11beta-hydroxylase transcription by steroidogenic factor-1. J Mol Endocrinol 2002; 28: 125\u2013135.","journal-title":"J Mol Endocrinol"},{"key":"BFjhh201224_CR36","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/01.hjh.0000254372.88488.a9","volume":"25","author":"S Sookoian","year":"2007","unstructured":"Sookoian S, Gianotti TF, Gonzalez CD, Pirola CJ . Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. J Hypertens 2007; 25: 5\u201313.","journal-title":"J Hypertens"},{"key":"BFjhh201224_CR37","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S0895-7061(99)00176-4","volume":"13","author":"S Patel","year":"2000","unstructured":"Patel S, Steeds R, Channer K, Samani NJ . Analysis of promoter region polymorphism in the aldosterone synthase gene (CYP11B2) as a risk factor for myocardial infarction. Am J Hypertens 2000; 13: 134\u2013139.","journal-title":"Am J Hypertens"},{"key":"BFjhh201224_CR38","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1016\/j.jacc.2006.07.030","volume":"48","author":"DM McNamara","year":"2006","unstructured":"McNamara DM, Tam SW, Sabolinski ML, Tobelmann P, Janosko K, Taylor AL et al. Aldosterone synthase promoter polymorphism predicts outcome in African Americans with heart failure: results from the A-HeFT Trial. J Am Coll Cardiol 2006; 48: 1277\u20131282.","journal-title":"J Am Coll Cardiol"}],"container-title":["Journal of Human Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/jhh201224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/jhh201224","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/jhh201224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T16:41:50Z","timestamp":1647535310000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/jhh201224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,28]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["BFjhh201224"],"URL":"https:\/\/doi.org\/10.1038\/jhh.2012.24","relation":{},"ISSN":["0950-9240","1476-5527"],"issn-type":[{"value":"0950-9240","type":"print"},{"value":"1476-5527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,28]]},"assertion":[{"value":"9 December 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2012","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2012","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2012","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}