Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects

Dongliang Ge, Haidong Zhu, Ying Huang, Frank A. Treiber, Gregory A Harshfield, Harold Snieder, Yanbin Dong

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A total of 920 young white and black twins (age: 12 to 30 years; 45% blacks) was subjected to three 10-minute stress tasks. Thirteen potential functional polymorphisms from 4 major RAAS genes were genotyped. We performed multilocus prediction allowing for genetic modification effects (gene-gene, gene-gender, gene-ethnicity, and gene-body mass index) using Multivariate Adaptive Regression Splines and generalized estimating equations. Single polymorphism analyses showed modest effects of M235T (angiotensinogen) and A-239T (angiotensin I-converting enzyme; P value range: 0.005 to 0.036), accounting for ≈1% of the total variance of systolic BP at rest and during stress. Compared with this, the best multilocus models revealed multiple independent genetic modification effects (gene-gene, gene-gender, and gene-body mass index; P value range: 0.003 to 0.009), accounting for 2.5% and 7.3% of the total variance for systolic BP levels at rest and during stress, respectively. Our data support the hypothesis that multiple RAAS genetic modifications account for BP variation. We conclude that the RAAS genetic modifications may contribute more to the dynamic BP regulation in response to behavioral stress compared with the static BP value. In addition, we reported a gene-gene interaction between M235T (angiotensinogen) and A1159G (angiotensin I-converting enzyme) on stress systolic BP levels. We proposed a viable approach to test for the multiple genetic contributions to BP and hypertension.

Original languageEnglish (US)
Pages (from-to)107-112
Number of pages6
JournalHypertension
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

Renin-Angiotensin System
Blood Pressure
Genes
Angiotensinogen
Peptidyl-Dipeptidase A
Body Mass Index
Hypertension

Keywords

  • Blacks
  • Blood pressure
  • Genetic modifications
  • Renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Multilocus analyses of renin-angiotensin-aldosterone system gene variants on blood pressure at rest and during behavioral stress in young normotensive subjects. / Ge, Dongliang; Zhu, Haidong; Huang, Ying; Treiber, Frank A.; Harshfield, Gregory A; Snieder, Harold; Dong, Yanbin.

In: Hypertension, Vol. 49, No. 1, 01.01.2007, p. 107-112.

Research output: Contribution to journalArticle

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abstract = "The renin-angiotensin-aldosterone system (RAAS) is a proteolytic cascade that regulates and maintains blood pressure (BP). This study aimed to explore the interactive and integrative effects of multiple RAAS polymorphisms on BP at rest and during behavioral stress in a normotensive population. A total of 920 young white and black twins (age: 12 to 30 years; 45{\%} blacks) was subjected to three 10-minute stress tasks. Thirteen potential functional polymorphisms from 4 major RAAS genes were genotyped. We performed multilocus prediction allowing for genetic modification effects (gene-gene, gene-gender, gene-ethnicity, and gene-body mass index) using Multivariate Adaptive Regression Splines and generalized estimating equations. Single polymorphism analyses showed modest effects of M235T (angiotensinogen) and A-239T (angiotensin I-converting enzyme; P value range: 0.005 to 0.036), accounting for ≈1{\%} of the total variance of systolic BP at rest and during stress. Compared with this, the best multilocus models revealed multiple independent genetic modification effects (gene-gene, gene-gender, and gene-body mass index; P value range: 0.003 to 0.009), accounting for 2.5{\%} and 7.3{\%} of the total variance for systolic BP levels at rest and during stress, respectively. Our data support the hypothesis that multiple RAAS genetic modifications account for BP variation. We conclude that the RAAS genetic modifications may contribute more to the dynamic BP regulation in response to behavioral stress compared with the static BP value. In addition, we reported a gene-gene interaction between M235T (angiotensinogen) and A1159G (angiotensin I-converting enzyme) on stress systolic BP levels. We proposed a viable approach to test for the multiple genetic contributions to BP and hypertension.",
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