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) 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.