Association of genetic variants in the apelin-APJ system and ACE2 with blood pressure responses to potassium supplementation: the GenSalt study

Am J Hypertens. 2010 Jun;23(6):606-13. doi: 10.1038/ajh.2010.36. Epub 2010 Mar 11.

Abstract

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.

Conclusion: Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2
  • Apelin
  • Apelin Receptors
  • Blood Pressure / genetics*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Molecular Epidemiology
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Single Nucleotide
  • Potassium, Dietary / administration & dosage
  • Potassium, Dietary / pharmacology*
  • Receptors, G-Protein-Coupled / genetics*
  • Sodium Chloride, Dietary / pharmacology

Substances

  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Intercellular Signaling Peptides and Proteins
  • Potassium, Dietary
  • Receptors, G-Protein-Coupled
  • Sodium Chloride, Dietary
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2