Document Detail


Renin gene polymorphisms and haplotypes, blood pressure, and responses to renin-angiotensin system inhibition.
MedLine Citation:
PMID:  17562974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-11
Journal Detail:
Title:  Hypertension     Volume:  50     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-08-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  340-7     Citation Subset:  IM    
Affiliation:
Molecular and Cellular Therapeutics, RCSI Research Institute, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
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MeSH Terms
Descriptor/Qualifier:
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:
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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