Document Detail

The epithelial sodium channel γ-subunit gene and blood pressure: family based association, renal gene expression, and physiological analyses.
MedLine Citation:
PMID:  22006290     Owner:  NLM     Status:  MEDLINE    
Variants in the gene encoding the γ-subunit of the epithelial sodium channel (SCNN1G) are associated with both Mendelian and quantitative effects on blood pressure. Here, in 4 cohorts of 1611 white European families composed of a total of 8199 individuals, we undertook staged testing of candidate single-nucleotide polymorphisms for SCNN1G (supplemented with imputation based on data from the 1000 Genomes Project) followed by a meta-analysis in all of the families of the strongest candidate. We also examined relationships between the genotypes and relevant intermediate renal phenotypes, as well as expression of SCNN1G in human kidneys. We found that an intronic single-nucleotide polymorphism of SCNN1G (rs13331086) was significantly associated with age-, sex-, and body mass index-adjusted blood pressure in each of the 4 populations (P<0.05). In an inverse variance-weighted meta-analysis of this single-nucleotide polymorphism in all 4 of the populations, each additional minor allele copy was associated with a 1-mm Hg increase in systolic blood pressure and 0.52-mm Hg increase in diastolic blood pressure (SE=0.33, P=0.002 for systolic blood pressure; SE=0.21, P=0.011 for diastolic blood pressure). The same allele was also associated with higher 12-hour overnight urinary potassium excretion (P=0.04), consistent with increased epithelial sodium channel activity. Renal samples from hypertensive subjects showed a nonsignificant (P=0.07) 1.7-fold higher expression of SCNN1G compared with normotensive controls. These data provide genetic and phenotypic evidence in support of a role for a common genetic variant of SCNN1G in blood pressure determination.
Cara J Büsst; Lisa D S Bloomer; Katrina J Scurrah; Justine A Ellis; Timothy A Barnes; Fadi J Charchar; Peter Braund; Paul N Hopkins; Nilesh J Samani; Steven C Hunt; Maciej Tomaszewski; Stephen B Harrap
Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-17
Journal Detail:
Title:  Hypertension     Volume:  58     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-18     Completed Date:  2012-01-03     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1073-8     Citation Subset:  IM    
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MeSH Terms
Blood Pressure / genetics*
Cohort Studies
Epithelial Sodium Channels / biosynthesis,  genetics*,  physiology
Europe / epidemiology,  ethnology
European Continental Ancestry Group / genetics
Gene Dosage
Gene Expression
Genetic Association Studies
Hypertension / epidemiology,  genetics
Introns / genetics
Kidney / metabolism
Middle Aged
Poland / epidemiology
Polymorphism, Single Nucleotide*
Potassium / urine*
Quantitative Trait Loci
RNA, Messenger / biosynthesis
Sodium / metabolism
Utah / epidemiology
Young Adult
Grant Support
AG18734/AG/NIA NIH HHS; HL21088/HL/NHLBI NIH HHS; HL24855/HL/NHLBI NIH HHS; HL44738/HL/NHLBI NIH HHS; R01 AG018734/AG/NIA NIH HHS; R01 AG018734-07/AG/NIA NIH HHS; R01 HL021088-14/HL/NHLBI NIH HHS; R01 HL024855-11/HL/NHLBI NIH HHS; R01 HL044738/HL/NHLBI NIH HHS; R01 HL044738-03/HL/NHLBI NIH HHS; //British Heart Foundation
Reg. No./Substance:
0/Epithelial Sodium Channels; 0/RNA, Messenger; 0/SCNN1G protein, human; 9NEZ333N27/Sodium; RWP5GA015D/Potassium
Comment In:
Hypertension. 2011 Dec;58(6):996-7   [PMID:  22006289 ]

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

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