{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T15:44:37Z","timestamp":1784562277881,"version":"3.55.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11]]},"abstract":"\n Background<\/jats:title>\n \n The majority of hypertensive individuals require combination antihypertensive therapy to achieve adequate blood pressure (\n BP<\/jats:styled-content>\n ) control. This study aimed to identify genetic variants associated with uncontrolled\n BP<\/jats:styled-content>\n on combination therapy with a thiazide diuretic and a \u03b2\u2010blocker.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n A genome\u2010wide association study of uncontrolled\n BP<\/jats:styled-content>\n on combination therapy was conducted among 314 white participants of the\n PEAR<\/jats:styled-content>\n (Pharmacogenomic Evaluation of Antihypertensive Responses) trial. Multivariable logistic regression analysis was used. Genetic variants meeting a suggestive level of significance (\n P<\/jats:italic>\n <1.0E\u201005) were tested for replication in an external cohort,\n INVEST<\/jats:styled-content>\n (International Verapamil\u2010\n SR<\/jats:styled-content>\n Trandolapril study). We also examined genome\u2010wide variant associations with systolic and diastolic\n BP<\/jats:styled-content>\n response on combination therapy and tested for replication. We discovered a single nucleotide polymorphism, the rs261316 major allele, at chromosome 15 in the gene\n ALDH1A2<\/jats:italic>\n associated with an increased odds of having uncontrolled\n BP<\/jats:styled-content>\n on combination therapy (odds ratio: 2.56, 95% confidence interval, 1.69\u20133.88,\n P<\/jats:italic>\n =8.64E\u201006). This single nucleotide polymorphism replicated (odds ratio: 1.86, 95% confidence interval, 1.35\u20132.57,\n P<\/jats:italic>\n =0.001) and approached genome\u2010wide significance in the meta\u2010analysis between discovery and replication cohorts (odds ratio: 2.16, 95% confidence interval, 1.63\u20132.86,\n P<\/jats:italic>\n =8.60E\u201008). Other genes in the region surrounding rs261316 (\n ALDH1A2)<\/jats:italic>\n include\n AQP9<\/jats:italic>\n and\n LIPC<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A single nucleotide polymorphism in the gene\n ALDH1A2<\/jats:italic>\n may be associated with uncontrolled\n BP<\/jats:styled-content>\n following treatment with a thiazide diuretic\/\u03b2\u2010blocker combination.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 00246519.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.006522","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:10:59Z","timestamp":1509667859000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic Variants Associated With Uncontrolled Blood Pressure on\u00a0Thiazide Diuretic\/\u03b2\u2010Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses)\u00a0and INVEST (International Verapamil\u2010SR Trandolapril Study) Trials"],"prefix":"10.1161","volume":"6","author":[{"given":"Oyunbileg","family":"Magvanjav","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, FL"},{"name":"College of Medicine, University of Florida, Gainesville, 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