| Renin gene polymorphisms and haplotypes, blood pressure, and responses to renin-angiotensin system inhibition. | |
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MedLine Citation:
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PMID: 17562974 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Renin catalyzes the rate-limiting step of the renin-angiotensin system. A T allele variant at position -5312 within a distal enhancer region has been reported to increase in vitro renin gene transcription. Among 387 White bank employees, ambulatory blood pressures were higher in 133 -5312T allele carriers than in 254 CC homozygotes-mean differences [99% confidence interval] between carriers and homozygotes for daytime and night-time systolic/diastolic pressure were 2.5[0.4,4.6]/1.7[0.2,3.2] and 2.4[0.5,4.4]/1.5[0.1,2.9] respectively. Ambulatory pressure estimates for the only common renin haplotype including the -5312T variant (-5312T, 5090C, 5912A, 9479A, 10194G), were statistically significantly higher than estimates for all other haplotypes. Among 259 White hypertensive participants in a randomized double-blind clinical trial comparing a renin antagonist, aliskiren, with an angiotensin receptor blocker, losartan, plasma renin activity did not differ with renin -5312C/T genotype. Nocturnal blood pressure reductions with losartan 100 mg daily were significantly greater in -5312T allele carriers than in CC homozygotes (mean[standard error]; -12.9[3.7]/-7.9[2.4] versus -7.1[2.5]/-4.2[1.6]) whereas with aliskiren 150 and 300 mg daily, lesser reductions were observed in -5312T allele carriers than in CC homozygotes (-5.4[2.0]/-4.1[1.3] versus -10.1[1.4]/-6.5[1.1]; P<0.03 for treatmentxgenotype interaction for night-time systolic and diastolic pressures). Hence, the -5312 renin C/T enhancer polymorphism does contribute to blood pressure variation in Whites and also appears to predict responses to inhibition of the renin-angiotensin system. These findings suggest that genotyping at this locus may aid in the identification of susceptibility to hypertension and in the selection of optimal therapy for individual hypertensive patients. |
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Authors:
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Niamh Moore; Patrick Dicker; John K O'Brien; Milos Stojanovic; Ronán M Conroy; Achim Treumann; Eoin T O'Brien; Desmond Fitzgerald; Denis Shields; Alice V Stanton |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-06-11 |
Journal Detail:
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Title: Hypertension Volume: 50 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-07-19 Completed Date: 2007-08-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 340-7 Citation Subset: IM |
Affiliation:
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Molecular and Cellular Therapeutics, RCSI Research Institute, Royal College of Surgeons in Ireland, Dublin 2, Ireland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Amides / therapeutic use Antihypertensive Agents / therapeutic use* Blood Pressure Monitoring, Ambulatory Chi-Square Distribution Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Female Follow-Up Studies Fumarates / therapeutic use Genetic Predisposition to Disease Haplotypes / genetics Humans Hypertension / diagnosis, drug therapy*, genetics* Linear Models Losartan / therapeutic use Male Middle Aged Multivariate Analysis Polymorphism, Genetic* Renin / genetics* Renin-Angiotensin System / drug effects*, genetics Severity of Illness Index Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Antihypertensive Agents; 0/Fumarates; 0/aliskiren; 114798-26-4/Losartan; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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