Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension

Roberto Pontremoli, Maura Ravera, Francesca Viazzi, Clizia Nicolella, Valeria Berruti, Giovanna Leoncini, Francesca Giacopelli, Gian Paolo Bezante, Giorgio Sacchi, Roberto Ravazzolo, Giacomo Deferrari

Research output: Contribution to journalArticle

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Abstract

Background. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). Methods. Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI ≥ 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). Results. The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 ± 0.5, DD; 8.2 ± 0.3, ID; 6.5 ± 0.4 IU/mL, II; P <0.0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df1 to 214, P <0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 ± 0.2, DD + ID; 0.8 ± 0.2 mg/mmol, II; P <0.006 by ANOVA) and bigger LVMI (124.1 ± 2.3, DD + ID vs. 117.8 ± 3.6 g/m2, II; P <0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5.22 for AT1; df1 to 214, P <0.02, for each one of the variables examined). Conclusion. The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.

Original languageEnglish
Pages (from-to)561-569
Number of pages9
JournalKidney International
Volume57
Issue number2
DOIs
Publication statusPublished - 2000

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Peptidyl-Dipeptidase A
Genetic Polymorphisms
Renin-Angiotensin System
Genotype
Albumins
Retinal Vessels
Creatinine
Analysis of Variance
Genes
Ophthalmoscopy
Albuminuria
Essential Hypertension
Serum
Cluster Analysis
Echocardiography
Body Mass Index
Cardiovascular Diseases
Alleles
Blood Pressure
Lipids

Keywords

  • ACE gene
  • Blood pressure
  • Cardiovascular disease
  • Microalbuminuria
  • Renin-angiotensin-aldosterone system

ASJC Scopus subject areas

  • Nephrology

Cite this

Pontremoli, R., Ravera, M., Viazzi, F., Nicolella, C., Berruti, V., Leoncini, G., ... Deferrari, G. (2000). Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension. Kidney International, 57(2), 561-569. https://doi.org/10.1046/j.1523-1755.2000.00876.x

Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension. / Pontremoli, Roberto; Ravera, Maura; Viazzi, Francesca; Nicolella, Clizia; Berruti, Valeria; Leoncini, Giovanna; Giacopelli, Francesca; Bezante, Gian Paolo; Sacchi, Giorgio; Ravazzolo, Roberto; Deferrari, Giacomo.

In: Kidney International, Vol. 57, No. 2, 2000, p. 561-569.

Research output: Contribution to journalArticle

Pontremoli, R, Ravera, M, Viazzi, F, Nicolella, C, Berruti, V, Leoncini, G, Giacopelli, F, Bezante, GP, Sacchi, G, Ravazzolo, R & Deferrari, G 2000, 'Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension', Kidney International, vol. 57, no. 2, pp. 561-569. https://doi.org/10.1046/j.1523-1755.2000.00876.x
Pontremoli, Roberto ; Ravera, Maura ; Viazzi, Francesca ; Nicolella, Clizia ; Berruti, Valeria ; Leoncini, Giovanna ; Giacopelli, Francesca ; Bezante, Gian Paolo ; Sacchi, Giorgio ; Ravazzolo, Roberto ; Deferrari, Giacomo. / Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension. In: Kidney International. 2000 ; Vol. 57, No. 2. pp. 561-569.
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author = "Roberto Pontremoli and Maura Ravera and Francesca Viazzi and Clizia Nicolella and Valeria Berruti and Giovanna Leoncini and Francesca Giacopelli and Bezante, {Gian Paolo} and Giorgio Sacchi and Roberto Ravazzolo and Giacomo Deferrari",
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TY - JOUR

T1 - Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension

AU - Pontremoli, Roberto

AU - Ravera, Maura

AU - Viazzi, Francesca

AU - Nicolella, Clizia

AU - Berruti, Valeria

AU - Leoncini, Giovanna

AU - Giacopelli, Francesca

AU - Bezante, Gian Paolo

AU - Sacchi, Giorgio

AU - Ravazzolo, Roberto

AU - Deferrari, Giacomo

PY - 2000

Y1 - 2000

N2 - Background. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). Methods. Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI ≥ 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). Results. The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 ± 0.5, DD; 8.2 ± 0.3, ID; 6.5 ± 0.4 IU/mL, II; P <0.0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df1 to 214, P <0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 ± 0.2, DD + ID; 0.8 ± 0.2 mg/mmol, II; P <0.006 by ANOVA) and bigger LVMI (124.1 ± 2.3, DD + ID vs. 117.8 ± 3.6 g/m2, II; P <0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5.22 for AT1; df1 to 214, P <0.02, for each one of the variables examined). Conclusion. The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.

AB - Background. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). Methods. Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI ≥ 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). Results. The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 ± 0.5, DD; 8.2 ± 0.3, ID; 6.5 ± 0.4 IU/mL, II; P <0.0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df1 to 214, P <0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 ± 0.2, DD + ID; 0.8 ± 0.2 mg/mmol, II; P <0.006 by ANOVA) and bigger LVMI (124.1 ± 2.3, DD + ID vs. 117.8 ± 3.6 g/m2, II; P <0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5.22 for AT1; df1 to 214, P <0.02, for each one of the variables examined). Conclusion. The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.

KW - ACE gene

KW - Blood pressure

KW - Cardiovascular disease

KW - Microalbuminuria

KW - Renin-angiotensin-aldosterone system

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