Genetic Determinants of Nonmodulating Hypertension

Natapong Kosachunhanun, Steven Hunt, Paul N. Hopkins, Roger R. Williams, Xavier Jeunemaitre, Pierre Corvol, Claudio Ferri, Richard M. Mortensen, Norman K. Hollenberg, Gordon H. Williams

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and χ2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 - 344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.

Original languageEnglish
Pages (from-to)901-908
Number of pages8
JournalHypertension
Volume42
Issue number5
DOIs
Publication statusPublished - Nov 2003
Externally publishedYes

Fingerprint

Angiotensinogen
Cytochrome P-450 CYP11B2
Peptidyl-Dipeptidase A
Hypertension
Odds Ratio
Genotype
Aldosterone
Phenotype
Linear Models
Genetic Epistasis
Angiotensin Type 1 Receptor
Angiotensins
Renin-Angiotensin System
Renin
Angiotensin II
Decision Making
Analysis of Variance
Confidence Intervals
Students
Genes

Keywords

  • Aldosterone
  • Gene expression
  • Genetics
  • Hypertension, genetic
  • Hypertension, nonmodulating

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Kosachunhanun, N., Hunt, S., Hopkins, P. N., Williams, R. R., Jeunemaitre, X., Corvol, P., ... Williams, G. H. (2003). Genetic Determinants of Nonmodulating Hypertension. Hypertension, 42(5), 901-908. https://doi.org/10.1161/01.HYP.0000095615.83724.82

Genetic Determinants of Nonmodulating Hypertension. / Kosachunhanun, Natapong; Hunt, Steven; Hopkins, Paul N.; Williams, Roger R.; Jeunemaitre, Xavier; Corvol, Pierre; Ferri, Claudio; Mortensen, Richard M.; Hollenberg, Norman K.; Williams, Gordon H.

In: Hypertension, Vol. 42, No. 5, 11.2003, p. 901-908.

Research output: Contribution to journalArticle

Kosachunhanun, N, Hunt, S, Hopkins, PN, Williams, RR, Jeunemaitre, X, Corvol, P, Ferri, C, Mortensen, RM, Hollenberg, NK & Williams, GH 2003, 'Genetic Determinants of Nonmodulating Hypertension', Hypertension, vol. 42, no. 5, pp. 901-908. https://doi.org/10.1161/01.HYP.0000095615.83724.82
Kosachunhanun N, Hunt S, Hopkins PN, Williams RR, Jeunemaitre X, Corvol P et al. Genetic Determinants of Nonmodulating Hypertension. Hypertension. 2003 Nov;42(5):901-908. https://doi.org/10.1161/01.HYP.0000095615.83724.82
Kosachunhanun, Natapong ; Hunt, Steven ; Hopkins, Paul N. ; Williams, Roger R. ; Jeunemaitre, Xavier ; Corvol, Pierre ; Ferri, Claudio ; Mortensen, Richard M. ; Hollenberg, Norman K. ; Williams, Gordon H. / Genetic Determinants of Nonmodulating Hypertension. In: Hypertension. 2003 ; Vol. 42, No. 5. pp. 901-908.
@article{4d0b1a5db705410c8bac07300fbc44c5,
title = "Genetic Determinants of Nonmodulating Hypertension",
abstract = "We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and χ2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 - 344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95{\%} confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.",
keywords = "Aldosterone, Gene expression, Genetics, Hypertension, genetic, Hypertension, nonmodulating",
author = "Natapong Kosachunhanun and Steven Hunt and Hopkins, {Paul N.} and Williams, {Roger R.} and Xavier Jeunemaitre and Pierre Corvol and Claudio Ferri and Mortensen, {Richard M.} and Hollenberg, {Norman K.} and Williams, {Gordon H.}",
year = "2003",
month = "11",
doi = "10.1161/01.HYP.0000095615.83724.82",
language = "English",
volume = "42",
pages = "901--908",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Genetic Determinants of Nonmodulating Hypertension

AU - Kosachunhanun, Natapong

AU - Hunt, Steven

AU - Hopkins, Paul N.

AU - Williams, Roger R.

AU - Jeunemaitre, Xavier

AU - Corvol, Pierre

AU - Ferri, Claudio

AU - Mortensen, Richard M.

AU - Hollenberg, Norman K.

AU - Williams, Gordon H.

PY - 2003/11

Y1 - 2003/11

N2 - We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and χ2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 - 344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.

AB - We sought to determine whether genes of the renin-angiotensin-aldosterone system can predict the nonmodulating intermediate phenotype in essential hypertension. Aldosterone responses to angiotensin II were assessed in 298 subjects with hypertension. Subjects were genotyped at the angiotensinogen M235T, angiotensin-converting enzyme I/D, aldosterone synthase C-344 T, renin, angiotensin II type 1 receptor, and adducin loci. The data were analyzed by Student t test, ANOVA, stepwise linear regression and general linear model or GENMOD regression techniques, and χ2 analysis odds ratios (ORs). Aldosterone response varied by genotype for angiotensin and aldosterone synthase but not for the other loci. The combination of angiotensinogen 235 TT and angiotensin-converting enzyme DD showed further reduction (P=0.0377) when compared with angiotensinogen 235 TT alone, an example of genetic epistasis. When the subject was required also to possess the CYP11B2 - 344 TT genotype, there was a further substantial reduction. Of these 3 loci, only angiotensinogen 235 TT significantly increased the OR of predicting the nonmodulating hypertensive phenotype (OR, 2.00; 95% confidence interval, 1.152 to 3.51). However, when angiotensin-converting enzyme DD was combined with angiotensinogen 235 TT, the OR nearly doubled to 3.74, with a further increase to 5.36-fold when the subject possessed all 3 genotypes. Thus, the angiotensinogen, angiotensin-converting enzyme, and aldosterone synthase genotypes identified individuals with the nonmodulating phenotype with an increasing degree of fidelity. For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making.

KW - Aldosterone

KW - Gene expression

KW - Genetics

KW - Hypertension, genetic

KW - Hypertension, nonmodulating

UR - http://www.scopus.com/inward/record.url?scp=0242693943&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242693943&partnerID=8YFLogxK

U2 - 10.1161/01.HYP.0000095615.83724.82

DO - 10.1161/01.HYP.0000095615.83724.82

M3 - Article

VL - 42

SP - 901

EP - 908

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -