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Genomic Association...
Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
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Turner, Stephen T. (author)
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Boerwinkle, Eric (author)
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O'Connell, Jeffrey R. (author)
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Bailey, Kent R. (author)
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Gong, Yan (author)
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Chapman, Arlene B. (author)
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McDonough, Caitrin W. (author)
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Beitelshees, Amber L. (author)
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Schwartz, Gary L. (author)
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Gums, John G. (author)
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Padmanabhan, Sandosh (author)
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Hiltunen, Timo P. (author)
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Citterio, Lorena (author)
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Donner, Kati M. (author)
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Hedner, Thomas (author)
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Lanzani, Chiara (author)
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Saarela, Janna (author)
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Ripatti, Samuli (author)
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Wahlstrand, Bjoern (author)
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Manunta, Paolo (author)
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Kontula, Kimmo (author)
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Dominiczak, Anna F. (author)
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Cooper-DeHoff, Rhonda M. (author)
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Johnson, Julie A. (author)
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(creator_code:org_t)
- 2013
- 2013
- English.
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In: Hypertension. - 1524-4563. ; 62:2, s. 391-397
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
Subject headings
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- To identify novel genes influencing blood pressure response to thiazide diuretic therapy for hypertension, we conducted genome-wide association meta-analyses of approximate to 1.1 million single-nucleotide polymorphisms in a combined sample of 424 European Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=228) and the Genetic Epidemiology of Responses to Antihypertensive study (n=196). Polymorphisms associated with blood pressure response at P<10(-5) were tested for replication of the associations in independent samples of hydrochlorothiazide-treated European hypertensives. The rs16960228 polymorphism in protein kinase C, replicated for same-direction association with diastolic blood pressure response in the Nordic Diltiazem study (n=420) and the Genetics of Drug Responsiveness in Essential Hypertension study (n=206), and the combined 4-study meta-analysis P value achieved genome-wide significance (P=3.3x10(-8)). Systolic or diastolic blood pressure responses were consistently greater in carriers of the rs16960228 A allele than in GG homozygotes (>4/4 mm Hg) across study samples. The rs2273359 polymorphism in the GNAS-EDN3 region also replicated for same-direction association with systolic blood pressure response in the Nordic Diltiazem study, and the combined 3-study meta-analysis P value approached genome-wide significance (P=5.5x10(-8)). The findings document clinically important effects of genetic variation at novel loci on blood pressure response to a thiazide diuretic, which may be a basis for individualization of antihypertensive drug therapy and identification of new drug targets.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- antihypertensive agents
- genomics
- hydrochlorothiazide
- hypertension
- pharmacogenomics
- protein kinase C
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Turner, Stephen ...
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Boerwinkle, Eric
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O'Connell, Jeffr ...
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Bailey, Kent R.
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Gong, Yan
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Chapman, Arlene ...
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show more...
-
McDonough, Caitr ...
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Beitelshees, Amb ...
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Schwartz, Gary L ...
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Gums, John G.
-
Padmanabhan, San ...
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Hiltunen, Timo P ...
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Citterio, Lorena
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Donner, Kati M.
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Hedner, Thomas
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Lanzani, Chiara
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Melander, Olle
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Saarela, Janna
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Ripatti, Samuli
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Wahlstrand, Bjoe ...
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Manunta, Paolo
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Kontula, Kimmo
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Dominiczak, Anna ...
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Cooper-DeHoff, R ...
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Johnson, Julie A ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Hypertension
- By the university
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Lund University