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 (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) 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% 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) mm Hg among men with minor G allele compared to those with major C allele of rs4646174, respectively.


CONCLUSIONS
Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA. qizhao@tulane.edu
Qi
Q
Zhao
Dongfeng
D
Gu
Tanika N
TN
Kelly
James E
JE
Hixson
Dabeeru C
DC
Rao
Cashell E
CE
Jaquish
Jing
J
Chen
Jianfeng
J
Huang
Chung-Shiuan
CS
Chen
C Charles
CC
Gu
Paul K
PK
Whelton
Jiang
J
He
D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D000073861:Apelin; D000075244:Apelin Receptors; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D017720:Molecular Epidemiology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D017419:Potassium, Dietary; D043562:Receptors, G-Protein-Coupled; D017673:Sodium Chloride, Dietary; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2