{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:07:18Z","timestamp":1790543238335,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T00:00:00Z","timestamp":1530489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01DK100306"],"award-info":[{"award-number":["R01DK100306"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"AMGEN","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cardiovascular mortality in patients receiving dialysis remains unacceptably high, with unexplained ancestry differences suggesting a genetic component.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed DNA samples from 37% of subjects enrolled in the EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE) trial, a randomized trial conducted in patients receiving hemodialysis with secondary hyperparathyroidism, comparing cinacalcet to placebo on a background of usual care. DNA was analyzed for single-nucleotide polymorphisms (SNPs) in the genes encoding the angiotensin-converting enzyme receptor type I (AGTR1) and angiotensin-converting enzyme (ACE). Survival analyses were conducted separately in European Ancestry (EA) and African Ancestry (AfAn) due to known differences in cardiovascular events, minor alleles for the same variant and the frequency of minor alleles. Our primary determination was a meta-analysis across both races.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Meta-analysis showed significant associations between rs5186 in AGTR1 and increased rates by 25\u201334% for the primary endpoint (composite of death or nonfatal myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event), all-cause mortality, cardiovascular mortality and heart failure; all P\u2009&amp;lt;\u20090.001. Three correlated SNPs in ACE were associated with lower rates of sudden cardiac death (SCD) in EA samples. One ACE SNP, rs4318, only found in the AfAn samples, was associated with a lower rate of SCD in the AfAn samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The C allele in rs5186 in AGTR1 was associated with higher rates of death and major cardiovascular events in a meta-analysis of EA and AfAn patients with end-stage kidney disease. SNPs in ACE were associated with SCD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfy191","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T15:22:24Z","timestamp":1528989744000},"page":"1924-1931","source":"Crossref","is-referenced-by-count":4,"title":["Angiotensin-related genetic determinants of cardiovascular disease in patients undergoing hemodialysis"],"prefix":"10.1093","volume":"34","author":[{"given":"Sharon M","family":"Moe","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Indiana University School of Medicine , Indianapolis, IN, USA"},{"name":"Department of Medicine, Roudebush Veterans Administration Medical Center , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Long","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine , Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Hwi Linus","family":"Schwantes-An","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S","family":"Decker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Wetherill","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J","family":"Edenberg","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Xuei","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Vatta","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana M","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine , Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn M","family":"Chertow","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Stanford University School of Medicine , Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,2]]},"reference":[{"key":"2025102312510138200_gfy191-B1","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1056\/NEJMoa1205624","article-title":"Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis","volume":"367","author":"Chertow","year":"2012","journal-title":"N Engl J Med"},{"key":"2025102312510138200_gfy191-B2","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1093\/ndt\/gfr777","article-title":"Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial","volume":"27","author":"Chertow","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"2025102312510138200_gfy191-B3","doi-asserted-by":"crossref","first-page":"e001363","DOI":"10.1161\/JAHA.114.001363","article-title":"Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial","volume":"3","author":"Wheeler","year":"2014","journal-title":"J Am Heart Assoc"},{"key":"2025102312510138200_gfy191-B4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1053\/j.ajkd.2005.11.018","article-title":"The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD","volume":"47","author":"Landray","year":"2006","journal-title":"Am J Kidney Dis"},{"key":"2025102312510138200_gfy191-B5","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1053\/j.ajkd.2004.11.015","article-title":"First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease","volume":"45","author":"Baigent","year":"2005","journal-title":"Am J Kidney Dis"},{"key":"2025102312510138200_gfy191-B6","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1093\/ndt\/gfl078","article-title":"Racial disparities in the prevalence of cardiovascular disease among incident end-stage renal disease patients","volume":"21","author":"Volkova","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"2025102312510138200_gfy191-B7","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1046\/j.1523-1755.2000.00285.x","article-title":"Racial differences in survival of patients on dialysis","volume":"58","author":"Pei","year":"2000","journal-title":"Kidney Int"},{"key":"2025102312510138200_gfy191-B8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5414\/CN108247","article-title":"Black ethnicity predicts better survival on dialysis despite greater deprivation and co-morbidity: a UK study","volume":"82","author":"Cole","year":"2014","journal-title":"Clin Nephrol"},{"key":"2025102312510138200_gfy191-B9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1525-139X.2005.18316.x","article-title":"Gene polymorphism association studies in dialysis: cardiovascular disease","volume":"18","author":"Rao","year":"2005","journal-title":"Semin Dial"},{"key":"2025102312510138200_gfy191-B10","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0140-6736(98)06434-4","article-title":"A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations","volume":"353","author":"Cole","year":"1999","journal-title":"Lancet"},{"key":"2025102312510138200_gfy191-B11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1172\/JCI0215219","article-title":"1, 25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system","volume":"110","author":"Li","year":"2002","journal-title":"J Clin Invest"},{"key":"2025102312510138200_gfy191-B12","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1161\/01.HYP.0000013734.33441.EA","article-title":"In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage","volume":"39","author":"Mitani","year":"2002","journal-title":"Hypertension"},{"key":"2025102312510138200_gfy191-B13","doi-asserted-by":"crossref","first-page":"F1168","DOI":"10.1152\/ajprenal.00606.2015","article-title":"FGF23 from bench to bedside","volume":"310","author":"Kovesdy","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"key":"2025102312510138200_gfy191-B14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.clinbiochem.2008.10.011","article-title":"Survival in type 2 diabetic patients in dialysis and the number of risk alleles in polymorphisms of the renin-angiotensin system genes","volume":"42","author":"Padro-Miquel","year":"2009","journal-title":"Clin Biochem"},{"key":"2025102312510138200_gfy191-B15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000064455","article-title":"Angiotensin II type 1 receptor gene polymorphism in end-stage renal disease","volume":"92","author":"Buraczynska","year":"2002","journal-title":"Nephron"},{"key":"2025102312510138200_gfy191-B16","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/j.1523-1755.2005.00510.x","article-title":"Renin-angiotensin polymorphisms and QTc interval prolongation in end-stage renal disease","volume":"68","author":"Raizada","year":"2005","journal-title":"Kidney Int"},{"key":"2025102312510138200_gfy191-B17","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1046\/j.1523-1755.1999.00770.x","article-title":"Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II","volume":"56","author":"Miller","year":"1999","journal-title":"Kidney Int"},{"key":"2025102312510138200_gfy191-B18","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1097\/HJH.0b013e32834494f6","article-title":"Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan","volume":"29","author":"Jiang","year":"2011","journal-title":"J Hypertens"},{"key":"2025102312510138200_gfy191-B19","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1097\/HJH.0b013e328330b654","article-title":"Adenine\/cytosine(1166) polymorphism of the angiotensin II type 1 receptor gene and the antihypertensive response to angiotensin-converting enzyme inhibitors","volume":"27","author":"Yu","year":"2009","journal-title":"J Hypertens"},{"key":"2025102312510138200_gfy191-B20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1086\/519979","article-title":"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","volume":"81","author":"Sethupathy","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2025102312510138200_gfy191-B21","doi-asserted-by":"crossref","first-page":"e64558","DOI":"10.1371\/journal.pone.0064558","article-title":"Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD)","volume":"8","author":"Chen","year":"2013","journal-title":"PLoS One"},{"key":"2025102312510138200_gfy191-B22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.112.006809","article-title":"A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme","volume":"65","author":"Bernstein","year":"2013","journal-title":"Pharmacol Rev"},{"key":"2025102312510138200_gfy191-B23","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1161\/01.HYP.27.1.62","article-title":"Racial difference in the relationship of an angiotensin I-converting enzyme gene polymorphism to serum angiotensin I-converting enzyme activity","volume":"27","author":"Bloem","year":"1996","journal-title":"Hypertension"},{"key":"2025102312510138200_gfy191-B24","doi-asserted-by":"crossref","first-page":"10063","DOI":"10.1007\/s11033-012-1875-6","article-title":"Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy: evidence from a meta-analysis","volume":"39","author":"Li","year":"2012","journal-title":"Mol Biol Rep"},{"key":"2025102312510138200_gfy191-B25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0272-6386(98)70126-X","article-title":"Insertion\/deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end-stage renal disease","volume":"32","author":"Osono","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"2025102312510138200_gfy191-B26","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/S0272-6386(04)00816-9","article-title":"Increased cardiovascular risk in long-term hemodialysis patients carrying deletion allele of ACE gene polymorphism","volume":"44","author":"Ishimitsu","year":"2004","journal-title":"Am J Kidney Dis"},{"key":"2025102312510138200_gfy191-B27","first-page":"209","article-title":"Survival and predictive factors of lethality in hemodialysis: D\/I polymorphism of the angiotensin I-converting enzyme and of the angiotensinogen M235T genes","volume":"103","author":"Alves","year":"2014","journal-title":"Arq Bras Cardiol"},{"key":"2025102312510138200_gfy191-B28","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/hmg\/10.10.1077","article-title":"Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE)","volume":"10","author":"McKenzie","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2025102312510138200_gfy191-B29","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/hmg\/ddg094","article-title":"Haplotypes extending across ACE are associated with Alzheimer's disease","volume":"12","author":"Kehoe","year":"2003","journal-title":"Hum Mol Genet"},{"key":"2025102312510138200_gfy191-B30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s00439-006-0191-4","article-title":"An angiotensin converting enzyme haplotype predicts survival in patients with end stage renal disease","volume":"120","author":"Wetmore","year":"2006","journal-title":"Hum Genet"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/34\/11\/1924\/30335793\/gfy191.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/34\/11\/1924\/30335793\/gfy191.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:52:23Z","timestamp":1761238343000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/34\/11\/1924\/5047848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,2]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,7,2]]},"published-print":{"date-parts":[[2019,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfy191","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2018,7,2]]}}}