Association of genetic variants in the apelin-APJ system and ace2 with blood pressure responses to potassium supplementation: The gensalt study

Background: Genetic factors may influence blood pressure (BP) responses to dietary potassium intake. We examined the association of genetic variants in the apelin-APJ system and angiotensin-converting enzyme 2 (ACE2) with BP responses to potassium supplementation. Methods: We conducted a 7-day potassium supplementation (60mmol/day) intervention among 1,906 Chinese adults who participated in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Tag single-nucleotide polymorphisms (SNPs) based on HapMap data and potential functional SNPs were selected in the APLN, APLNR, and ACE2 genes. Because the ACE2 and APLN genes are located on the X chromosome, men and women were analyzed separately. Results: In women, SNP rs2235306 in the APLN gene was significantly associated with diastolic BP (DBP) response to potassium supplementation (P = 0.0009). The DBP responses (95% confidence interval (CI)) among those with genotypes T/T, T/C, and C/C were-2.22 (-2.74,-1.70),-1.69 (-2.20,-1.19), and-0.81 (-1.54,-0.09) mmHg, respectively. In men, SNP rs4646174 of the ACE2 gene was significantly associated with systolic BP (SBP), DBP, and mean arterial pressure (MAP) responses to potassium supplementation (P = 0.0001, P = 0.001, and P = 3.0 × 10^-6, respectively). The SBP, DBP, and MAP responses (95% CI) were-0.79 (-2.27, 0.69) vs.-3.53 (-3.94,-3.12), 1.07 (-0.34, 2.49) vs.-1.06 (-1.43,-0.69), and 0.44 (-0.60, 1.48) vs.-1.89 (-2.22,-1.55) mmHg among men with minor G allele compared to those with major C allele of rs4646174, respectively. Conclusion Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.