Abstract MP68: Common Genetic Variants in the Endothelial System Predict Blood Pressure Response to Sodium Intake: The GenSalt Study
Recent evidence suggests that the role of the endothelial system in blood pressure (BP) regulation may in part be mediated by endothelial nitric oxide response to extracellular sodium concentrations. Despite these data, few studies have explored the relationship between endothelial system genes and BP responses to dietary sodium intake. In the current study, we examined the association between 292 common genetic variants from fourteen endothelial system genes and BP salt-sensitivity among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. A 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding-study (307.8 mmol sodium/day) was conducted among 1,906 GenSalt participants from 633 Han Chinese families. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. Additive associations between each SNP and BP responses to low and high-sodium interventions were assessed using a mixed linear regression model to account for familial dependencies. The false discovery rate method was used to adjust for multiple testing. Systolic BP (SBP) and mean arterial pressure (MAP) responses to low-sodium decreased with the number of DDAH1 rs11161637 G alleles (both P-values=2×10-4). Participants with genotypes A/A, A/G, and G/G had SBP responses of -6.20 (-6.70, -5.70), -5.38 (-5.87, -4.88), and -4.02 (-5.33, -2.70) mmHg, respectively; and MAP responses of -4.08 (-4.47, -3.69), -3.43 (-3.83, -3.04) and -2.45 (-3.42, -1.48) mmHg, respectively. Diastolic BP (DBP) and MAP responses to low-sodium increased with each copy of the VWF rs2239153 C allele (both P-values=1×10-4). For genotypes T/T, T/C, and C/C, DBP responses were -2.13 (-2.55, -1.72), -3.09 (-3.54,-2.64), and -3.38 (-4.08, -2.67) mmHg, respectively; and MAP responses were -3.13 (-3.54, -2.73), -4.08 (-4.51, -3.65), and -4.43 (-5.11, -3.76) mmHg, respectively. We observed an inverse dose-allele relationship between the COL18A1 rs2838944 variant and DBP and MAP responses to high-sodium (P-values=1×10-4 and 2×10-4, respectively). Among participants with G/G, G/A, and A/A genotypes, DBP responses were 1.83 (1.52, 2.14), 0.65 (0.00, 1.29), and -1.03 (-3.45, 1.38) mmHg, respectively, and MAP responses were 2.78 (2.50, 3.07), 1.72 (1.13, 2.31), and -0.04 (-1.81, 1.72) mmHg, respectively. Our study provides the first evidence for a role of endothelial system genes DDAH1, VWF, and COL18A1 in the etiology of BP salt-sensitivity. Replication and functional studies will be needed to confirm these findings.
- © 2013 by American Heart Association, Inc.