Association of Genetic Variants in the Apelin–APJ System and ACE2 With Blood Pressure Responses to Potassium Supplementation: The GenSalt Study

• Published in: American journal of hypertension Vol. 23; no. 6; pp. 606 - 613
• Main Authors: Zhao, Qi, Gu, Dongfeng, Kelly, Tanika N., Hixson, James E., Rao, Dabeeru C., Jaquish, Cashell E., Chen, Jing, Huang, Jianfeng, Chen, Chung-Shiuan, Gu, C. Charles, Whelton, Paul K., He, Jiang
• Format: Journal Article
• Language: English
• Published: Basingstoke Oxford University Press 01.06.2010; Nature Publishing Group
• Subjects: ACE2; ACE2 gene; Adult; Apelin; apelin receptor; Apelin Receptors; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; blood pressure; Blood Pressure - genetics; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Female; Humans; hypertension; Intercellular Signaling Peptides and Proteins - genetics; Male; Medical sciences; Molecular Epidemiology; Peptidyl-Dipeptidase A - genetics; polymorphism; Polymorphism, Single Nucleotide; potassium supplement; Potassium, Dietary - administration & dosage; Potassium, Dietary - pharmacology; Receptors, G-Protein-Coupled - genetics; Sodium Chloride, Dietary - pharmacology; ACE2; blood pressure; apelin; potassium supplement; apelin receptor; polymorphism; hypertension; Hypertension; 4CE2; Genetic variant; Cardiovascular disease; Inorganic element; Arterial pressure; Blood pressure; Supplementation; Potassium; Polymorphism
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2010.36

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.