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Genetic variants in the reninangiotensinaldosterone system and blood pressure responses to potassium intake

He, Jianga,b,*; Gu, Dongfengc,*; Kelly, Tanika N.a; Hixson, James E.d; Rao, Dabeeru C.e; Jaquish, Cashell E.f; Chen, Jing; Zhao, Qia; Gu, Chic,e; Huang, Jianfengc; Shimmin, Lawrence C.d; Chen, Ji-Chunb,c; Mu, Jianjung; Ji, Xuh; Liu, De-Peii; Whelton, Paul K.j; for the GenSalt Collaborative Research Group

Journal of Hypertension:
doi: 10.1097/HJH.0b013e32834a4d1f
Original papers: Genetic aspects
Abstract

Objective: Observational epidemiologic studies and clinical trials have documented that dietary potassium intake lowers blood pressure (BP). We examined the association between genetic variants in the renin–angiotensin–aldosterone system and BP responses to potassium intervention.

Methods: A 7-day high-sodium followed by a 7-day high-sodium plus 60 mmol/day potassium-supplementation feeding study was conducted among 1906 participants from rural northern China. Nine BP measurements were obtained at each intervention phase using a random-zero sphygmomanometer and 181 single-nucleotide polymorphisms (SNPs) in 11 candidate genes of the renin–angiotensin–aldosterone system were used for analyses.

Results: Several SNPs in nuclear receptor subfamily 3, group C, member 2 (NR3C2), angiotensin II type 1 receptor (AGTR1), hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1), and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) genes were significantly associated with BP responses to potassium intervention. For example, the number of G alleles of the N554S missense mutation (rs5527) of NR3C2 was significantly associated with greater SBP responses to potassium intervention; mean [95% confidence interval (CI)] responses (mmHg) were −3.33 (−3.65 to −3.02) for genotype A/A and −5.47 (−6.64 to −4.29) for A/G, respectively (P value = 0.0004). In addition, the number of C alleles of the A1166C variant (rs5186) in AGTR1 was significantly and inversely associated with SBP responses to potassium intervention; mean (95% CI) responses were −3.55 (−3.87 to −3.24) for genotype A/A, −2.45 (−3.27 to −1.62) for A/C, and 3.25 (−5.73 to 12.23) for CC (P value = 0.003).

Conclusion: These novel findings indicated that genetic variants in the renin–angiotensin–aldosterone system may play an important role in determining an individual's BP responses to dietary potassium intake.

Author Information

aDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine

bDepartment of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA

cFuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Disease, Beijing, China

dHuman Genetic Center, University of Texas School of Public Health, Houston, Texas

eDivision of Biostatistics, Washington University School of Medicine, St Louis, Missouri

fDivision of Cardiovascular Sciences, National Heart, Lung, Blood Institute, Bethesda, Maryland, USA

gDepartment of Medicine, Xi’an Jiaotong University School of Medicine, Shanxi

hXinle Traditional Chinese Medicine Hospital, Hebei

iNational Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

jOffice of the President, Loyola University Medical Center, Maywood, Illinois, USA

*Jiang He and Dongfeng Gu contributed equally to the writing of this article.

Correspondence to Jiang He, MD, PhD, Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2000, New Orleans, LA 70112, USA Tel: +1 504 988 5165; fax: +1 504 988 1568; e-mail: jhe@tulane.edu

Abbreviations: ACE, angiotensin-converting enzyme; AGT, angiotensinogen; AGTR1, angiotensin II type 1 receptor; AGTR2, angiotensin II type 1 receptor 2; BP, blood pressure; CI, confidence interval; CYP11B1, cytochrome P450, family 11, subfamily B, polypeptide 1; CYP11B2, cytochrome P450, family 11, subfamily B, polypeptide 2; FDR, false discovery rate; GenSalt, Genetic Epidemiology Network of Salt Sensitivity; HSD11B1, hydroxysteroid (11-beta) dehydrogenase 1; HSD11B2, hydroxysteroid (11-beta) dehydrogenase 2; MAP, mean arterial pressure; NR3C2, nuclear receptor subfamily 3, group C, member 2; REN, renin; RENBP, renin-binding protein

Received 28 January, 2011

Revised 6 May, 2011

Accepted 27 June, 2011

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© 2011 Lippincott Williams & Wilkins, Inc.