Impact of Renin-Angiotensin System Polymorphisms on Development of Systolic Dysfunction in Hypertrophic Cardiomyopathy  - Evidence From a Study of Genotyped Patients -

Funada, Akira; Konno, Tetsuo; Fujino, Noboru; Muramoto, Akihiko; Hayashi, Kenshi; Tsubokawa, Toshinari; Sakata, Kenji; Kawashiri, Masa‐aki; Takeda, Yoshiyu; Ino, Hidekazu; Yamagishi, Masakazu

doi:10.1253/circj.cj-10-0482

Cited by 18 publications

(8 citation statements)

References 34 publications

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“…93 Furthermore, it has been observed, in a novel study, that the presence of these two polymorphisms together causes an increase in RAAS activity, which is closely related to myocardial hypertrophy and subsequent left ventricular remodelling. 94 However, these results were not confirmed by one study in Caucasians. 39 On the other hand, the impact of six proLVH polymorphism in RAAS (ACE deletion, AGT M235T, AGT T174M, AGTR1 A1166C, AGTR2 A3123C, CYP11B2 -344C>T and CMA B -1903G>A) in the appearance of fibrosis in patients with HCM was tested.…”

Section: Effect Of Several Pro-lvh Raas Polymorphismsmentioning

confidence: 74%

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

Orenes‐Piñero

Hernández-Romero

Jover

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening. Microscopically it is characterised by cardiomyocyte hypertrophy, myofibrillar disarray and fibrosis. The phenotypic expression of HCM is multifactorial, with the majority of cases occurring secondary to mutations in genes encoding the sarcomere proteins. In conjunction with the genetic heterogeneity of HCM, phenotypic expression also exhibits a high level of variability even within families with the same aetiological mutation, and may be influenced by additional genetic factors. Polymorphisms of the renin-angiotensin-aldosterone system (RAAS) represent an attractive hypothesis as potential disease modifiers, as these genetic variants alter the 'activation status' of the RAAS, which leads to more left ventricular hypertrophy through different pathways. The main objective of this review is to provide an overview of the role of different polymorphisms identified in the RAAS, in patients with HCM.

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Section: Effect Of Several Pro-lvh Raas Polymorphismsmentioning

confidence: 74%

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

Orenes‐Piñero

Hernández-Romero

Jover

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…Mutations in genes encoding z-disc proteins,3 calcium handling proteins,4 or involved in protein degradation5 have also been related to the pathogenesis of the disease and can explain an additional relatively small number of HCM cases. Furthermore, polymorphisms in genes of the renin–angiotensin system,6 7 in the resistin gene,8 and in the MEF2C gene,9 among others, have been described as modifiers in HCM features, with controversial results in some cases 10. These findings support the search for additional genes implicated in the pathophysiology of HCM or in the interindividual variability 11.…”

Section: Introductionmentioning

confidence: 80%

Rare Genetic Variants in Gata Transcription Factors in Patients with Hypertrophic Cardiomyopathy

Alonso-Montes

Rodríguez‐Reguero

Martı́n

et al. 2017

Journal of Investigative Medicine

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Hypertrophic cardiomyopathy (HCM) is a very heterogeneous disease. Although primarily caused by mutations in genes encoding sarcomeric proteins, other genes might explain that heterogeneity. Potential candidate genes are GATA transcription factors that regulate the expression of proteins associated with HCM. Exons of ,, and genes were sequenced in 212 patients with unrelated HCM previously analyzed for genes encoding the most frequently mutated sarcomeric proteins. Functional effects of variants were predicted by in silico analyses. 3 potentially pathogenic variants were identified: c.-77G>A in , p.Ala343Thr (rs370588269) in, and p.Pro555Ala (rs146243018) in Multivariate analyses showed that angina was more frequent in patients carrying sarcomeric and GATA rare variants (55% vs 23.2% in non-carriers of GATA rare variants, OR (95% CI) 7.12 (1.23 to 41.27), p=0.029). Among patients without a known causal mutation, GATA rare variants were associated with a greater maximum posterior wall thickness (16.4±4.4 vs 14.0±3.1 mm in non-carriers, p=0.021). Thus, variants having a putative effect on GATA genes would alter the expression of their target genes and could modify the hypertrophic response. Therefore, although relatively infrequent in patients with HCM, they may represent a novel insight into the molecular mechanisms related to the pathogenesis of HCM.

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“…A study of genetic variants on human chromosome 22 has suggested that humans harbor a similar level of INDELs [32]. Recent evidence has indicated that angiotensin-converting enzyme (ACE) INDELs were associated with hypertension [33], diabetes mellitus [34], hypertrophic cardiomyopathy [35], and coronary heart disease [36]. However, the association between ACE INDELs and stroke has failed to be established [37,38].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants in the Promoter Region of the <i>ALOX5AP</i> Gene and Susceptibility of Ischemic Stroke

Jia

et al. 2011

Cerebrovasc Dis

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Background: Despite accumulating evidence supporting the association between variants of the ALOX5AP gene and atherosclerotic vascular events, the precise mechanism is still unclear. No variants in the coding sequence that lead to amino acid substitution have been found. We investigated genetic variants in the promoter region of the ALOX5AP gene and the association with ischemic stroke in a north Chinese Han population. Methods: 505 cases of ischemic stroke and 500 age- and gender-matched controls of the north Chinese Han population were enrolled. Genetic variants in the promoter region of the ALOX5AP gene were identified by polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were randomly selected and compared for serum leukotriene B₄ (LTB₄) concentration. The effect on ischemic stroke was evaluated by logistic regression. Results: Three genetic variants were identified, including a mutation (–519 G > A), an insertion and deletion polymorphisms (–581_582 Ins A) and a single nuclear polymorphisms (–946 A > G). Association study showed that the II genotype of –581_582 Ins A was significantly associated with ischemic stroke of a large artery atherosclerosis (OR = 3.50, 95% CI = 1.93–6.36, p = 0.0002) and undetermined etiology (OR = 3.66, 95% CI = 1.92–6.94, p = 0.0006). No significant association was found between the –519 GA genotype (OR = 0.35, 95% CI = 0.02–5.88, p = 0.46), –946 AG genotype (OR = 1.35, 95% CI = 0.85–2.16, p = 0.21) and ischemic stroke. There was no significant difference in serum LTB₄ concentration between cases (n = 40) and controls (n = 40) (log serum LTB₄ of cases vs. controls: 2.67 ± 0.14 vs. 2.73 ± 0.18 pg/ml, p = 0.10). However, the serum LTB₄ concentration was significantly higher in participants with the II genotype of –581_582 Ins A (n = 12) than that of participants with the DD genotype (n = 68) (log serum LTB₄ of participants with II genotype vs. DD genotype: 2.82 ± 0.18 vs. 2.68 ± 0.15 pg/ml, p = 0.01). Conclusion: The –581_582 Ins A polymorphism might be a novel genetic risk factor for ischemic stroke in a north Chinese Han population. Further studies on molecular mechanism are warranted.

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Impact of Renin-Angiotensin System Polymorphisms on Development of Systolic Dysfunction in Hypertrophic Cardiomyopathy - Evidence From a Study of Genotyped Patients -

Cited by 18 publications

References 34 publications

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

Rare Genetic Variants in Gata Transcription Factors in Patients with Hypertrophic Cardiomyopathy

Genetic Variants in the Promoter Region of the <i>ALOX5AP</i> Gene and Susceptibility of Ischemic Stroke

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