Common genetic variants in the endothelial system predict blood pressure response to sodium intake: The gensalt study

Maria Daniela Defagó, Dongfeng Gu, James E. Hixson, Lawrence C. Shimmin, Treva K. Rice, Charles C. Gu, Cashell E. Jaquish, De Pei Liu, Jiang He, Tanika N. Kelly

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)643-656
Number of pages14
JournalAmerican Journal of Hypertension
Issue number5
StatePublished - May 2013


  • blood pressure
  • endothelial system
  • genes
  • hypertension
  • salt sensitivity


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