{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:44:54Z","timestamp":1780451094736,"version":"3.54.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Thiazide diuretics are the second most frequently prescribed class of antihypertensives, but up to 50% of patients with hypertension have minimal antihypertensive response to thiazides. We explored circulating microRNAs (miRNAs) in search of predictive biomarkers of thiazide response.<\/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 profiled 754 miRNAs in baseline plasma samples of 36 hypertensive European American adults treated with hydrochlorothiazide, categorized into responders (n=18) and nonresponders (n=18) on the basis of diastolic blood pressure response to hydrochlorothiazide. miRNAs with \u22652.5\u2010fold differential expression between responders and nonresponders were considered for validation in 3 cohorts (n=50 each): hydrochlorothiazide\u2010treated European Americans, chlorthalidone\u2010treated European Americans, and hydrochlorothiazide\u2010treated Black individuals. Different blood pressure phenotypes including categorical (responder versus nonresponder) and continuous diastolic blood pressure and systolic blood pressure were tested for association with the candidate miRNA expression using multivariate regression analyses adjusting for age, sex, and baseline blood pressure. After quality control, 74 miRNAs were available for screening, 19 of which were considered for validation. In the validation cohort, miR\u2010193b\u20103p and 30d\u20105p showed significant associations with continuous SBP or diastolic blood pressure\u00a0response or both, to hydrochlorothiazide in European Americans at Benjamini\u2010Hochberg adjusted\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05. In the combined analysis of validation cohorts, let\u20107g (odds ratio, 0.6 [95% CI, 0.4\u20130.8]), miR\u2010142\u20103p (odds ratio, 1.1 [95% CI, 1.0, 1.2]), and miR\u2010423\u20105p (odds ratio, 0.7 [95% CI, 0.5\u20130.9]) associated with categorical diastolic blood pressure response at Benjamini\u2010Hochberg adjusted\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05. Predicted target genes of the 5 miRNAs were mapped to key hypertension pathways: lysine degradation, fatty acid biosynthesis, and metabolism.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The above identified circulating miRNAs may have a potential for clinical use as biomarkers for thiazide diuretic selection in hypertension.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>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:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n              . Unique identifiers:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00246519\">NCT00246519<\/jats:ext-link>\n              ,\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01203852\">NCT01203852<\/jats:ext-link>\n              ,\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00005520\">NCT00005520<\/jats:ext-link>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.032433","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T11:29:15Z","timestamp":1707910155000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating microRNA Biomarkers of Thiazide Response in Hypertension"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-9180","authenticated-orcid":false,"given":"Lakshmi Manasa S.","family":"Chekka","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-1093","authenticated-orcid":false,"given":"Marwa","family":"Tantawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research 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Microbiology, College of Medicine University of Florida Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlene B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Division of Nephrology University of Chicago Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-9566","authenticated-orcid":false,"given":"John G.","family":"Gums","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-0544","authenticated-orcid":false,"given":"Eric","family":"Boerwinkle","sequence":"additional","affiliation":[{"name":"University of Texas at Houston Center for Human Genetics Houston 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