Document Detail


Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.
MedLine Citation:
PMID:  22987918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2012-09-17
Journal Detail:
Title:  Hypertension     Volume:  60     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-01-10     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1359-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
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 HL084236/HL/NHLBI NIH HHS; K23-HL-084236/HL/NHLBI NIH HHS; M01 RR002635/RR/NCRR 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 HL092196/HL/NHLBI NIH HHS; R01 HL095796/HL/NHLBI NIH HHS; R01-HL-092196/HL/NHLBI NIH HHS; T32 DK007646/DK/NIDDK NIH HHS; T32 HL007609/HL/NHLBI 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:
0/SLC4A5 protein, human; 0/Sodium Chloride, Dietary; 0/Sodium-Bicarbonate Symporters; 4964P6T9RB/Aldosterone; EC 3.4.23.15/Renin
Comments/Corrections

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