Common Genetic Variants in the Endothelial System Predict Blood Pressure Response to Sodium Intake: The GenSalt Study

BACKGROUND We examined the association between 14 endothelial system genes and salt-sensitivity of blood pressure (BP). METHODS After a 3-day baseline examination, during which time the usual diet was consumed, 1,906 Chinese participants received a 7-day low-sodium diet (51.3 mmol of sodium/day) fol...

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Bibliographic Details
Published in:American journal of hypertension 2013-05, Vol.26 (5), p.643-656
Main Authors: Defagó, Maria Daniela, Gu, Dongfeng, Hixson, James E., Shimmin, Lawrence C., Rice, Treva K., Gu, Charles C., Jaquish, Cashell E., Liu, De-Pei, He, Jiang, Kelly, Tanika N.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Alleles
Amidohydrolases - genetics
Asian Continental Ancestry Group
Blood Pressure - drug effects
Blood Pressure - genetics
Blood Pressure - physiology
Diet, Sodium-Restricted
E-Selectin - genetics
Endothelium, Vascular - physiology
Female
Fibril-Associated Collagens - genetics
Genetic Variation - genetics
Genotype
Humans
Male
Middle Aged
Original
Sex Factors
Sodium, Dietary - pharmacology
von Willebrand Factor - genetics
Young Adult
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Summary:BACKGROUND We examined the association between 14 endothelial system genes and salt-sensitivity of blood pressure (BP). METHODS After a 3-day baseline examination, during which time the usual diet was consumed, 1,906 Chinese participants received a 7-day low-sodium diet (51.3 mmol of sodium/day) followed by a 7-day high-sodium diet (307.8 mmol of sodium/day). BP measurements were obtained at baseline and at the end of each intervention using a random-zero sphygmomanometer. RESULTS The DDAH1 rs11161637 variant was associated with reduced BP salt sensitivity, conferring attenuated systolic BP (SBP) and mean arterial pressure (MAP) decreases from baseline to the low-sodium intervention (both P = 2×10−4). Examination of genotype-sex interactions revealed that this relation was driven by the strong associations observed in men (P for interactions = 1.10×10−4 and 0.008, respectively). When switching from the low- to high-sodium intervention, increases in diastolic BP (DBP) and MAP were attenuated by the COL18A1 rs2838944 minor A allele (P = 1.41×10−4 and 1.55×10−4, respectively). Conversely, the VWF rs2239153 C variant was associated with increased salt sensitivity, conferring larger DBP and MAP reductions during low-sodium intervention (P = 1.22×10−4 and 4.44×10−5, respectively). Ten variants from 3 independent SELE loci displayed significant genotype-sex interactions on DBP and MAP responses to low-sodium (P for interaction = 1.56×10−3 to 1.00×10−4). Among men, minor alleles of 4 correlated markers attenuated BP responses to low-sodium intake, whereas minor alleles of another 4 correlated markers increased BP responses. No associations were observed in women for these variants. Further, qualitative interactions were shown for 2 correlated SELE markers. CONCLUSIONS These data support a role for the endothelial system genes in salt sensitivity.
ISSN:0895-7061
1941-7225
DOI:10.1093/ajh/hps099