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 (60 mmol/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 (Cl)) 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) mm Hg, 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 x 10(-6), respectively). The SBP, DBP, and MAP responses (95% Cl) 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) mm Hg 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.