Genotypic interactions of renin–angiotensin system genes in myocardial infarction

Araújo, Messias Antônio; Goulart, Luiz Ricardo; Cordeiro, Elisângela Rosa; Gatti, R; Menezes, Bruno Soares; Lourenço, Clauber; Silva, Heyder Diniz

doi:10.1016/j.ijcard.2004.07.009

Cited by 41 publications

(31 citation statements)

References 29 publications

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“…23 Although Canavy et al found that the genotype distribution of AT1R polymorphism was significantly different between controls and patients, 27 studies of the association between the C allele and coronary disease have been inconclusive. 28,29 Our data are in agreement with these reports, demonstrating that A/C1166 polymorphism was not associated with AMI. Positive associations between this polymorphism and disease may be the result of linkage disequilibrium with another polymorphism of functional importance, either within the AT1R gene or one nearby.…”

Section: 7±04 Ns No Significant Difference Was Found Among Three Gesupporting

confidence: 93%

Association Between A/C1166 Gene Polymorphism of the Angiotensin II Type 1 Receptor and Biventricular Functions in Patients With Acute Myocardial Infarction

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et al. 2006

Circ J

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cute myocardial infarction (AMI) is characterized by loss of contractile tissue and changes in ventricular geometry. 1 The presence of congestive heart failure or left ventricular (LV) systolic dysfunction is probably the most important risk factor in patients with AMI. 2 The development of right ventricular (RV) dysfunction has been reported following LV myocardial infarction (MI), 3,4 and is also associated with increased risk of shock, arrhythmia, and death. 5,6 After MI, the process of LV remodeling begins rapidly, usually within the first few hours after an infarct, and continues to progress. 7 Furthermore, it is known that the renin -angiotensin -aldosterone system (RAS) and angiotensin-converting enzyme (ACE) activity contribute to the remodeling process. 8 Angiotensin II (ATII) is the final effector of the RAS. It is a vasoactive peptide and leads to growth promotion, fibroblast proliferation, and the most potent vasoactive and salt-retaining effector peptide of the RAS, which is involved in blood pressure homeostasis and cardiovascular pathophysiology. Two subtypes of cell surface receptors, ATII type 1 receptor (AT1R) and ATII type 2 receptor Circulation Journal Vol. 70, October 2006 (AT2R), have been identified. Most of the actions of ATII are mediated by AT1, which is particularly prominent in the myocardium. 9,10 Although a number of polymorphisms of the AT1R gene have been identified, one of the most widely studied is an A-C substitution at position 1166 (A/C1166). 11 Two-dimensional (D) and Doppler echocardiography is a reliable tool for the diagnosis of systolic and diastolic dysfunction. The Doppler echocardiographic myocardial performance index (MPI) called the "Tei index", combining time intervals of LV contraction and relaxation, has been shown to be a powerful predictor of death and congestive heart failure after MI. 12,13 This index can be obtained easily, is reproducible and independent of the ventricular geometry, and has been shown to have potential for clinical application in the assessment of overall cardiac function in various disorders. 14 Poulsen et al recently reported that the LVMPI was a powerful predictor of death or congestive heart failure after MI, 15 and Moller et al showed that the RVMPI was increased in the acute phase of MI and was significantly correlated with indices of RV systolic dysfunction. 16 In a previous study, we reported higher LVMPI and RVMPI in patients with the DD genotype than in patients with the ID genotype of the ACE gene after anterior AMI. 17 Although there have been several association studies of the polymorphism of AT1R (A/C1166) in clinical endpoints, such as MI, 18 hypertension, 11 aortic stiffness, 19 and LV mass, 20 to our knowledge the relationship between AT1R polymorphism and biventricular function in anterior Methods and ResultsThe study group comprised 132 consecutive patients who were admitted to the coronary care unit with their first acute anterior MI. Systolic and diastolic diameters, volumes, inflow properties, ejection fraction an...

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Section: 7±04 Ns No Significant Difference Was Found Among Three Gesupporting

confidence: 93%

Association Between A/C1166 Gene Polymorphism of the Angiotensin II Type 1 Receptor and Biventricular Functions in Patients With Acute Myocardial Infarction

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Öztürk

Yazıcı

et al. 2006

Circ J

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“…Those 18 investigations 18-35 contained 6794 cases and 6204 controls, including 11 studies of Caucasians, [18][19][20][21][22][23][24][25][26][27][28] three studies of Asians, 29,30,35 two studies of Africans, 31,34 one study in the population of Durban in South Africa, 32 and one study in the Brazilian population. 33 The average frequency of C allele distribution in patients with MI for overall populations was 24.74% and the average frequency in controls was 22.58%. The average frequency of C allele distribution in Caucasians was 29.43% in cases and 27.83% for controls.…”

Section: Study Characteristics For MImentioning

confidence: 90%

A systematic review and meta-analysis of the association between angiotensin II type 1 receptor A1166C gene polymorphism and myocardial infarction susceptibility

Zheng

Shi

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Background and aim: Many reported studies have been conducted to investigate the association of angiotensin II type 1 receptor (AT1R) A1166C gene polymorphism with myocardial infarction (MI) susceptibility. However, the results from those reports are still conflicting. This meta-analysis was performed to study the relationship between AT1R A1166C gene polymorphism and MI risk. Method: The databases of PubMed, Embase, and Cochrane Library were searched as of 1 March 2012, and eligible investigations were recruited into this meta-analysis. Results: Eighteen investigations were identified for the analysis of association between AT1R A1166C gene polymorphism and MI risk, 11 in Caucasians, three in Asians, two in Africans, one in the population of Brazil and one in the population of Durban, South Africa . There was a marked association between AT1R C allele and MI susceptibility for overall populations (odds ratio (OR)=1.12, 95% confidence interval (CI): 1.01-1.25, p=0.03), and AT1R AA genotype was associated with a lower risk of MI in overall populations (OR=0.87, 95% CI: 0.78-0.98, p=0.02). However, AT1R A1166C gene polymorphism was not associated with MI risk in the sub-groups of Caucasians, Asians, Africans, Brazil and Durban populations. Conclusions: C allele is a risk factor for the MI susceptibility in overall populations, and AA genotype might be a protective factor against the MI risk in overall populations. However, more case-control association investigations on larger, stratified populations are required in the future.

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“…Although the potential effects of gene-gene or gene-risk factor interactions were not tested, the study underlined the important effects of a combination of polymorphic variants at different RAAS loci on cardiovascular phenotypic expression even in the absence of detectable individual effects at each locus. Recently, studies have shown that the interactions between RAAS genes were related to myocardial infarction 27 and renal insufficiency. 28 However, several questions remain unanswered, for example, how much of the individual difference of BP could be explained by the RAAS polymorphisms and their interactions as a whole?…”

Section: Discussionmentioning

confidence: 99%

Multilocus Analyses of Renin–Angiotensin–Aldosterone System Gene Variants on Blood Pressure at Rest and During Behavioral Stress in Young Normotensive Subjects

Zhu

Huang

et al. 2007

Hypertension

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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 Ϸ1% 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. Key Words: genetic modifications Ⅲ blood pressure Ⅲ blacks Ⅲ renin-angiotensin-aldosterone system T he renin-angiotensin-aldosterone system (RAAS), a proteolytic cascade that influences all aspects of blood pressure (BP) including blood vessel contraction and electrolyte homeostasis, 1,2 continues to dominate the interest of investigators in the field of genetics of essential hypertension. To this date, however, findings from association studies involving the RAAS genes remain inconsistent and controversial. This article aimed to revisit the contribution of polymorphisms of the RAAS genes to the determination of BP.There are Ն2 major reasons to conduct the present study. First, BP is a multifactorial trait, which is not based on single genes of major effects, but on interactions between genes. There are sizable genetic modifications (nonadditive interactions) among a relatively small network of genes, 3 such as the RAAS. Genetic modifications may also be expressed by the interactions between genes and hypertension risk factors, such as ethnicity, gender, and body mass index (BMI). Recently, genetic modifications have been considered ubiquitous components for the genetic architecture of complex traits. Furthermore, the complex gene-gene interac...

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Genotypic interactions of renin–angiotensin system genes in myocardial infarction

Cited by 41 publications

References 29 publications

Association Between A/C1166 Gene Polymorphism of the Angiotensin II Type 1 Receptor and Biventricular Functions in Patients With Acute Myocardial Infarction

Association Between A/C1166 Gene Polymorphism of the Angiotensin II Type 1 Receptor and Biventricular Functions in Patients With Acute Myocardial Infarction

A systematic review and meta-analysis of the association between angiotensin II type 1 receptor A1166C gene polymorphism and myocardial infarction susceptibility

Multilocus Analyses of Renin–Angiotensin–Aldosterone System Gene Variants on Blood Pressure at Rest and During Behavioral Stress in Young Normotensive Subjects

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