An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy

Tiago, Armindo; Badenhorst, Danelle; Skudicky, Daniel; Woodiwiss, Angela J.; Candy, Geoffrey P.; Brooksbank, Richard; Sliwa, Karen; Sareli, Pinhas; Norton, Gavin R.

doi:10.1016/s0008-6363(02)00281-x

Cited by 42 publications

(39 citation statements)

References 18 publications

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“…11 The genotype distributions among the controls of all studies were consistent with HWE except for one study. 11 Of the six retrospective studies, four papers used population-based controls, [11][12][13][14] and two studies of one paper used hospital-based controls. 15 The study by Goldbergova et al 12 used the mismatch method, and the other studies used polymerase chain reaction/restriction fragment length polymorphism for genotyping.…”

Section: Resultsmentioning

confidence: 59%

The M235T polymorphism in the angiotensinogen gene and heart failure: a meta-analysis

Chen

Zhang

Wang³

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Background: The aim of the present study was to assess the association between M235T polymorphism and heart failure using a meta-analysis. Methods: A literature search of Google Scholar, PubMed, the Cochrane Library and the China National Knowledge Infrastructure database (January 1990-April 2012) was performed for relevant studies. Statistical analyses were carried out using the Stata 12.0 to combine all the relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed under the allelic contrast (T vs M), the dominant (TT + MT vs. MM) and the recessive models (TT vs MT + MM). Begg's test was used to measure publication bias. Results: A total of six case-control studies including 842 patients and 1054 controls were enrolled in this meta-analysis. Overall, there was a significant association between angiotensinogen (AGT) gene M235T polymorphism and risk of heart failure in the subgroup analysis under the allelic contrast (T vs M: OR = 1.48, 95% CI: 1.04-2.11) and the dominant model (TT+MT vs MM: OR=1.67, 95% CI: 1.13-2.46) in the Caucasian population. Conclusions:The current meta-analysis suggests that M235T polymorphism might be associated with increased risk of heart failure in Caucasians.

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Section: Resultsmentioning

confidence: 59%

The M235T polymorphism in the angiotensinogen gene and heart failure: a meta-analysis

Chen

Zhang

Wang³

et al. 2012

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

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“…Most studies did not find an association between the ACE polymorphism and heart failure secondary to ischemic and/or dilated cardiomyopathy in 1506 Caucasian, [23][24][25][26] 287 Chinese, 27 281 Japanese, 28 and 724 black South African subjects. 29,30 Hence, it seems unlikely that susceptibility to ischemic or idiopathic dilated cardiomyopathy in the general population is associated with the ACE I/D polymorphism.…”

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…Candy et al 30 found an association between DD genotype and reduced cardiac function and increased cavity size in South African patients with cardiomyopathy, whereas others did not. 29 The first study on the ACE polymorphism and hypertrophic cardiomyopathy found an excess of DD genotype in Caucasian patients, especially in families with a history of sudden cardiac death. 36 Other studies have since then confirmed the higher frequency of DD genotype in hypertrophic cardiomyopathy in white and Japanese patients.…”

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

“…50 Nevertheless, most studies did not find an association between the M235T polymorphism and development or progression of ischemic and dilated cardiomyopathy. 25,28,29,35 Therefore, it is unlikely that this polymorphism plays a role in these disorders. An increased risk of heart failure in subjects carrying both 235M/T and Ϫ6G/G genotypes has been reported, however, suggesting the presence of a diseaserelated haplotype.…”

Section: Angiotensinogen M235t Polymorphismmentioning

confidence: 99%

“…71 This finding could not be confirmed in black South Africans with heart failure. 29 Studies in hypertrophic cardiomyopathy also yielded conflicting results. 42,72 Consequently, there is no firm evidence for a role of this polymorphism in heart failure.…”

Section: Aldosterone Synthase C-344t Polymorphismmentioning

confidence: 99%

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Genetic polymorphisms and heart failure

Bleumink

Schut

Sturkenboom

et al. 2004

Genetics in Medicine

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Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism.Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system.Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study Heart failure is a complex clinical syndrome with high morbidity and mortality. 1,2 Impairment of cardiac function activates compensatory neurohormonal mechanisms, which at a later stage may accelerate progression of heart failure. 3 Coronary heart disease and hypertension are major underlying causes of heart failure. Other frequent underlying conditions include valvular heart disease and idiopathic dilated cardiomyopathy. It is difficult to predict who will develop heart failure in response to myocardial injury. Racial differences in occurrence and outcome of heart failure 4,5 and heritability estimates of variability in left ventricular mass of 28% to 65% 6,7 suggest a genetic contribution to the pathophysiology of left ventricular remodeling and heart failure.Many studies have been published on the role of single gene mutations in (familial) cardiomyopathies. 8,9 These Mendelian traits are by nature rare, and although important at an individual level and for the understanding of disease mechanisms, are of limited significance in terms of prediction of heart failure occurrence in the population. 10 Moreover, in patients with identical gene mutations clinical manifestations of cardiomyopathy may differ. This suggests that probably also environmental and/or other genetic factors play a role.In this report, genetic polymorphisms of major neurohormonal systems involved in the pathophysiology of heart failure will be discussed, including the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous...

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Pharmacogenomics of Heart Failure

Lymperopoulos

French

2014

Methods in Molecular Biology

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The combination of angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor (βAR) blockers remains the essential component of heart failure (HF) pharmacotherapy. However, individual patient responses to these pharmacotherapies vary widely. The variability in response cannot be explained entirely by clinical characteristics, and genetic variation may play a role. The purpose of this chapter is to examine the current knowledge in the field of beta-blocker and ACE inhibitor pharmacogenetics in HF. β-blocker and ACE inhibitor pharmacogenetic studies performed in patients with HF were identified from the PubMed database from 1966 to July 2011. Thirty beta-blocker and 10 ACE inhibitor pharmacogenetic studies in patients with HF were identified.The ACE deletion variant was associated with greater survival benefit from ACE inhibitors and beta-blockers compared with the ACE insertion. Ser49 in the β1AR, the insertion in the α2CAR, and Gln41 in G protein-coupled receptor (GPCR) kinase (GRK)-5 are associated with greater survival benefit from β-blockers, compared with Gly49, the deletion, and Leu41, respectively. However, many of these associations have not been validated. The HF pharmacogenetic literature is still in its very early stages, but there are promising candidate genetic variants that may identify which HF patients are most likely to benefit from beta-blockers and ACE inhibitors and patients that may require additional therapies.

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An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy

Abstract: A CYP11B2 gene variant predicts the variable improvement in LV ejection fraction that occurs subsequent to initiating medical therapy in IDC. These data suggest a role for the aldosterone synthase locus in regulating the progression of heart failure.

Cited by 42 publications

References 18 publications

The M235T polymorphism in the angiotensinogen gene and heart failure: a meta-analysis

The M235T polymorphism in the angiotensinogen gene and heart failure: a meta-analysis

Genetic polymorphisms and heart failure

Pharmacogenomics of Heart Failure

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