| The Epithelial Sodium Channel {gamma}-Subunit Gene and Blood Pressure: Family Based Association, Renal Gene Expression, and Physiological Analyses. | |
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MedLine Citation:
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PMID: 22006290 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-10-17 |
Journal Detail:
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Title: Hypertension Volume: - ISSN: 1524-4563 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Physiology and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia; Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; School of Science and Engineering, University of Ballarat, Ballarat, Victoria, Australia; Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT; Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom; Current address: Paris Cardiovascular Research Centre, Institut National de la Santé et de la Recherche Médicale U970, Paris, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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