| Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. | |
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MedLine Citation:
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PMID: 22987918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations. |
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Authors:
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Robert M Carey; Cynthia D Schoeffel; John J Gildea; John E Jones; Helen E McGrath; Lindsay N Gordon; Min Jeong Park; Rafal S Sobota; Patricia C Underwood; Jonathan Williams; Bei Sun; Benjamin Raby; Jessica Lasky-Su; Paul N Hopkins; Gail K Adler; Scott M Williams; Pedro A Jose; Robin A Felder |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural Date: 2012-09-17 |
Journal Detail:
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Title: Hypertension Volume: 60 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-18 Completed Date: 2013-01-10 Revised Date: 2013-04-16 |
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: 1359-66 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908-1414, USA. rmc4c@virginia.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aldosterone / blood Blood Pressure / genetics*, physiology Body Mass Index Diet Dose-Response Relationship, Drug Female Gene Frequency Genetic Predisposition to Disease / genetics* Genotype Humans Hypertension / etiology, genetics*, physiopathology Logistic Models Male Meta-Analysis as Topic Middle Aged Odds Ratio Outcome Assessment (Health Care) Polymorphism, Single Nucleotide* Renin / blood Sodium Chloride, Dietary / administration & dosage, adverse effects Sodium-Bicarbonate Symporters / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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F31-NR011108/NR/NINR NIH HHS; F32 NR013318/NR/NINR NIH HHS; HL-47651/HL/NHLBI NIH HHS; HL-59424/HL/NHLBI NIH HHS; K23-HL-084236/HL/NHLBI NIH HHS; M01-RR02635/RR/NCRR NIH HHS; P01 HL074940/HL/NHLBI NIH HHS; P01-HL-074940/HL/NHLBI NIH HHS; P50-HL-055000/HL/NHLBI NIH HHS; R01 HL095796/HL/NHLBI NIH HHS; R01-HL-092196/HL/NHLBI NIH HHS; T32 DK007646/DK/NIDDK NIH HHS; T32-GM-080178/GM/NIGMS NIH HHS; T32-HL-007609/HL/NHLBI NIH HHS; U54LM008748/LM/NLM NIH HHS; UL1RR025758/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/SLC4A5 protein, human; 0/Sodium Chloride, Dietary; 0/Sodium-Bicarbonate Symporters; 52-39-1/Aldosterone; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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