| A pharmacogenetic analysis of determinants of hypertension and blood pressure response to angiotensin-converting enzyme inhibitor therapy in patients with vascular disease and healthy individuals. | |
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MedLine Citation:
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PMID: 21157371 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS: To investigate whether genetic variation in the renin-angiotensin-aldosterone system (RAAS) and kallikrein-bradykinin pathways is related to hypertension and blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitor therapy in stable coronary artery disease (CAD) patients. METHODS AND RESULTS: In 8907 stable CAD patients from the EUROPA trial, 52 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 12 candidate genes within the RAAS and kallikrein-bradykinin pathways were investigated for association with hypertension (defined as BP ≥160/95 mmHg or use of antihypertensives) and BP response to ACE inhibitors, during a 4-week run-in period. All analyses were adjusted for age, sex, body mass index and creatinine clearance and corrected for multiple testing. RESULTS: Hypertension was present in 28.3% of the patients (n = 2526); median BP reduction after perindopril was 10/4 mmHg. Four polymorphisms, located in the ACE (rs4291), angiotensinogen (rs5049) and (pro)renin receptor (rs2968915; rs5981008) genes were significantly associated with hypertension in two vascular disease populations of CAD (EUROPA) and cerebrovascular disease (PROGRESS; n = 3571). A cumulative profile demonstrated a stepwise increase in the prevalence of hypertension, mounting to a 2-3-fold increase (P for trend <0.001). Similar associations on hypertension were observed for angiotensinogen in a healthy population (n = 2197). In addition, genetic polymorphisms were identified that significantly modified the BP reduction by ACE inhibitor therapy; however, the observed BP differences were small and did not remain significant after permutation analysis. CONCLUSION: This large genetic association study identified genetic determinants of hypertension in three cohorts of patients with vascular disease and healthy individuals. |
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Authors:
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Jasper J Brugts; Aaron Isaacs; Moniek Pm de Maat; Eric Boersma; Cock M van Duijn; K Martijn Akkerhuis; Andre G Uitterlinden; Jacqueline Cm Witteman; Francois Cambien; Claudio Ceconi; Willem Remme; Michel Bertrand; Toshiharu Ninomiya; Stephen Harrap; John Chalmers; Stephen Macmahon; Kim Fox; Roberto Ferrari; Maarten L Simoons; Ah Jan Danser |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-13 |
Journal Detail:
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Title: Journal of hypertension Volume: - ISSN: 1473-5598 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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aDepartment of Cardiology, The Netherlands bDepartment of Genetic Epidemiology, The Netherlands cDepartment of Haematology, The Netherlands dDepartment of Internal Medicine, The Netherlands eDepartment of Epidemiology & Biostatistics of the Erasmus MC, Rotterdam, The Netherlands. fINSERM, Paris, France gUniversity of Ferrara, and Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy hSTICARES Cardiovascular Research, Rhoon, The Netherlands iLille Heart Institute, Lille, France jThe George Institute, University of Sydney and Royal Prince Alfred Hospital, Sydney kThe University of Melbourne, Melbourne, Australia lRoyal Brompton and National Heart Institute, London, UK. |
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