{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:33:00Z","timestamp":1783629180664,"version":"3.55.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,12,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Resistant hypertension (RHTN), defined by lack of blood pressure (BP) control despite treatment with at least 3 antihypertensive drugs, increases cardiovascular risk compared with controlled hypertension. Yet, there are few data on genetic variants associated with RHTN.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We used a gene\u2010centric array containing \u224850\u00a0000 single\u2010nucleotide polymorphisms (SNPs) to identify polymorphisms associated with RHTN in hypertensive participants with coronary artery disease (CAD) from INVEST\u2010GENES (the INnternational VErapamil\u2010SR Trandolapril STudy\u2014GENEtic Substudy). RHTN was defined as BP\u2265140\/90 on 3 drugs, or any BP on 4 or more drugs. Logistic regression analysis was performed in European Americans (n=904) and Hispanics (n=837), using an additive model adjusted for age, gender, randomized treatment assignment, body mass index, principal components for ancestry, and other significant predictors of RHTN. Replication of the top SNP was conducted in 241 European American women from WISE (Women's Ischemia Syndrome Evaluation), where RHTN was defined similarly. To investigate the functional effect of rs12817819, mRNA expression was measured in whole blood. We found\n              <jats:italic>ATP2B1<\/jats:italic>\n              rs12817819 associated with RHTN in both INVEST European Americans (\n              <jats:italic>P<\/jats:italic>\n              \u2010value=2.44\u00d710\n              <jats:sup>\u22123<\/jats:sup>\n              , odds ratio=1.57 [1.17 to 2.01]) and INVEST Hispanics (\n              <jats:italic>P<\/jats:italic>\n              =7.69\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              , odds ratio=1.76 [1.27 to 2.44]). A consistent trend was observed at rs12817819 in WISE, and the INVEST\u2010WISE meta\u2010analysis result reached chip\u2010wide significance (\n              <jats:italic>P<\/jats:italic>\n              =1.60\u00d710\n              <jats:sup>\u22126<\/jats:sup>\n              , odds ratio=1.65 [1.36 to 1.95]). Expression analyses revealed significant differences in ATP2B1 expression by rs12817819 genotype.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The\n              <jats:italic>ATP2B1<\/jats:italic>\n              rs12817819 A allele is associated with increased risk for RHTN in hypertensive participants with documented CAD or suspected ischemic heart disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifiers: NCT00133692 (INVEST), NCT00000554 (WISE).\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001398","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T06:32:15Z","timestamp":1415687535000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Large\u2010Scale Gene\u2010Centric Analysis Identifies Polymorphisms for Resistant Hypertension"],"prefix":"10.1161","volume":"3","author":[{"given":"Vanessa","family":"Fontana","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitrin W.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal M.","family":"El Rouby","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Caroline C.","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute Harbor\u2010UCLA Medical Center, Torrance, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u2010D. Ida","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute Harbor\u2010UCLA Medical Center, Torrance, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Gums","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"},{"name":"Department of Community Health and Family Medicine, University of Florida College of Medicine, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"The Renal Division, Department of Medicine, Emory University, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Turner","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Pepine","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda M.","family":"Cooper\u2010DeHoff","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, 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