Document Detail


Common variants in genes underlying monogenic hypertension and hypotension and blood pressure in the general population.
MedLine Citation:
PMID:  18443236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The genes responsible for several monogenic hypertensive and hypotensive disorders have been identified. Our aim was to evaluate whether common variants in these genes affect blood pressure in the general population. We studied 2037 adults from 520 nuclear families characterized for 24-hour ambulatory blood pressure and related cardiovascular traits. We genotyped 298 tagging and putative functional single nucleotide polymorphisms, achieving a median coverage of 82.4% across 11 candidate loci. Five polymorphisms in the KCNJ1 gene coding for the potassium channel, ROMK, showed associations with mean 24-hour systolic or diastolic blood pressure. The strongest association was with an intronic polymorphism, rs2846679, where the minor allele (frequency 16%) was associated with a -1.58 (95% CI -2.47 to -0.69) mm Hg change in mean 24-hour systolic blood pressure, after accounting for age, sex, and familial correlations (P=0.00048). Polymorphisms in the gene were also associated with clinic blood pressure and left ventricular mass as assessed by ECG Sokolow-Lyon voltage (P=0.0081 for rs675759). Associations with mean 24-hour systolic or diastolic blood pressure were also observed for variants in CASR, NR3C2, SCNN1B, and SCNN1G. The findings show that common variants in genes responsible for some Mendelian disorders of hypertension and hypotension affect blood pressure in the general population. Notably, variants in KCNJ1, which causes Bartter syndrome type 2, were strongly associated, potentially providing a novel target for intervention.
Authors:
Martin D Tobin; Maciej Tomaszewski; Peter S Braund; Cother Hajat; Stuart M Raleigh; Thomas M Palmer; Mark Caulfield; Paul R Burton; Nilesh J Samani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-28
Journal Detail:
Title:  Hypertension     Volume:  51     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-23     Completed Date:  2008-06-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1658-64     Citation Subset:  IM    
Affiliation:
Department of Health Sciences & Genetics, University of Leicester, UK.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Blood Pressure / genetics
Epithelial Sodium Channel / genetics
Family Health
Female
Genetic Predisposition to Disease / epidemiology
Genetic Variation*
Genotype
Humans
Hypertension / epidemiology,  genetics*
Hypotension / epidemiology,  genetics*
Male
Middle Aged
Polymorphism, Single Nucleotide
Potassium Channels, Inwardly Rectifying / genetics*
Receptors, Calcium-Sensing / genetics
Receptors, Mineralocorticoid / genetics
Risk Factors
Grant Support
ID/Acronym/Agency:
G0501942//Medical Research Council; //British Heart Foundation; //Wellcome Trust
Chemical
Reg. No./Substance:
0/CASR protein, human; 0/Epithelial Sodium Channel; 0/KCNJ1 protein, human; 0/Potassium Channels, Inwardly Rectifying; 0/Receptors, Calcium-Sensing; 0/Receptors, Mineralocorticoid; 0/SCNN1B protein, human; 0/SCNN1G protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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