Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy

Ishanov, Alisher; Okamoto, Hiroshi; Yoneya, Keiji; Watanabe, Masashi; Izumi, Namiki; Machida, Maiko; Onozuka, Hisao; Mikami, Taisei; Kawaguchi, Hideaki; Hata, Akira; Kondo, Kiyotaro; Kitabatake, Akira

doi:10.1016/s0002-8703(97)70207-2

Cited by 42 publications

(31 citation statements)

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“…13,14 The T4C (p.M235T) polymorphism in the AGT gene has been described as a predisposing factor for cardiac hypertrophy in patients with hypertension, in endurance athletes and in sporadic cases of HCM. [21][22][23] Furthermore, Ortlepp et al 13 found an association between the CC genotype of this polymorphism with increased left ventricular mass and increased IVS thickness. The AGT gene encodes angiotensinogen and the C-allele of this polymorphism is associated with elevated AGT serum concentrations.…”

Section: Discussionmentioning

confidence: 99%

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

et al. 2012

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The phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are candidates for modifying phenotypic expression. In order to investigate whether RAAS polymorphisms modulate HCM phenotype, we selected a large cohort of carriers of one of the three functionally equivalent truncating mutations in the MYBPC3 gene. Family-based association analysis was performed to analyze the effects of five candidate RAAS polymorphisms (ACE, rs4646994; AGTR1, rs5186; CMA, rs1800875; AGT, rs699; CYP11B2, rs1799998) in 368 subjects carrying one of the three mutations in the MYBPC3 gene. Interventricular septum (IVS) thickness and Wigle score were assessed by 2D-echocardiography. SNPs in the RAAS system were analyzed separately and combined as a pro-left ventricular hypertrophy (LVH) score for effects on the HCM phenotype. Analyzing the five polymorphisms separately for effects on IVS thickness and Wigle score detected two modest associations. Carriers of the CC genotype in the AGT gene had less pronounced IVS thickness compared with CT and TT genotype carriers. The DD polymorphism in the ACE gene was associated with a high Wigle score (P ¼ 0.01). No association was detected between the pro-LVH score and IVS thickness or Wigle score. In conclusion, in contrast to previous studies, in our large study population of HCM patients with functionally equivalent mutations in the MYBPC3 gene we did not find major effects of genetic variation within the genes of the RAAS system on phenotypic expression of HCM.

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Section: Discussionmentioning

confidence: 99%

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

et al. 2012

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“…In Japanese subjects, one study revealed a higher frequency of the 235T allele in hypertrophic cardiomyopathy. 38 This could not be confirmed by others. 28 A study by Ortlepp and colleagues in 26 family members carrying a single mutation in the MyBP-C gene revealed a significant association between the angiotensinogen polymorphism and cardiac hypertrophy.…”

Section: Angiotensinogen M235t Polymorphismmentioning

confidence: 73%

“…Frequency and outcome of heart failure differ significantly between races, 4,5 as do allele frequencies of genetic polymorphisms. 28,35,38,80 Nearly all populations are confounded by genetic admixture at some level. 104 Lack of replicability of an association in different ethnic groups does not rule out the possibility of a causal association, because of potentially different background risks, allele frequencies, and environmental factors.…”

Section: Discussionmentioning

confidence: 99%

“…36 Other studies have since then confirmed the higher frequency of DD genotype in hypertrophic cardiomyopathy in white and Japanese patients. [37][38][39] Yamada et al 28 did not detect an association between ACE genotypes and hypertrophic cardiomyopathy in Japanese. In addition, no association was found between ACE genotypes and echocardiographic measurements.…”

Section: Renin-angiotensin-aldosterone Systemmentioning

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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“…Uma das características mais notáveis da doença é a sua heterogeneidade fenotípica, (7)(8)(9) que pode ser causada em pelo menos dois loci e isso foi visto a partir da existência de um gene localizado no braço largo do cromossoma 14, na banda mais próxima do centrômero e foi denominado FHC-1. Descobriu-se posteriormente que este gen codifica a cadeia pesada de miosina.…”

Section: Introductionunclassified

A redução do gradiente na via de saída do ventrículo esquerdo pelo marcapasso DDD em pacientes com miocardiopatia hipertrófica obstrutiva

Faes¹,

Sant'Anna²,

Prates³

et al. 2002

Rev Bras Cir Cardiovasc

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Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy

Cited by 42 publications

References 22 publications

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

The role of renin–angiotensin–aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

Genetic polymorphisms and heart failure

A redução do gradiente na via de saída do ventrículo esquerdo pelo marcapasso DDD em pacientes com miocardiopatia hipertrófica obstrutiva

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