Dataset Information

Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study.

ABSTRACT: BACKGROUND:Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome", is a type of heart failure characterized by transient ventricular dysfunction in the absence of obstructive coronary lesions. Although associated with increased levels of catecholamines, pathophysiological mechanisms are unknown. Relapses and family heritability indicate a genetic predisposition. Several small studies have investigated associations between three different loci; the ?1-adrenic receptor (ADRB1), G-protein-coupled receptor kinase 5 (GRK5), Bcl-associated athanogene 3 (BAG3) and TCM but no consensus has been reached. METHODS:Participants were recruited using the Swedish Coronary Angiography and Angioplasty Register (SCAAR). TCM patients without coronary artery disease (CAD)(n?=?258) were identified and age- and sex-matched subjects with (n?=?164) and without (n?=?243) CAD were selected as controls. DNA was isolated from saliva and genotyped for candidate single nucleotide polymorphisms in the ADRB1, GRK5 and BAG3 genes. Allele frequencies and Odds Ratios (OR) with 95% Confidence Intervals (CI) for the investigated polymorphisms were compared, respectively calculated for TCM patients and controls. RESULTS:There were no differences in allele frequencies between TCM patients and controls. OR (CI) for TCM patients having at least one minor allele using controls as reference were 1.07 (0.75-1.55) for ADRB1, 0.45 (0.11-1.85) for GRK5 and 1.27 (0.74-2.19) for BAG3. CONCLUSION:By genotyping a large takotsubo cohort, we demonstrate a lack of association between candidate SNPs in the ADRB1, GRK5 and BAG3 genes, earlier suggested to contribute to TCM. Our result indicates a need to expand the search for new genetic candidates contributing to TCM.

SUBMITTER: Mattsson E

PROVIDER: S-EPMC5842616 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study.

Mattsson Emma E Saliba-Gustafsson Peter P Ehrenborg Ewa E Tornvall Per P

BMC medical genetics 20180307 1

<h4>Background</h4>Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome", is a type of heart failure characterized by transient ventricular dysfunction in the absence of obstructive coronary lesions. Although associated with increased levels of catecholamines, pathophysiological mechanisms are unknown. Relapses and family heritability indicate a genetic predisposition. Several small studies have investigated associations between three different loci; the β1-adrenic receptor (ADRB ...[more]

PMID: 29514624

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Project description:BACKGROUND: Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. OBJECTIVE: This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. DATA SOURCES: A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. REVIEW METHODS: The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. RESULTS: Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203-214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027-1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858-865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472-479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. CONCLUSION: Whether an emotional or physical event precedes one's symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.

Project description:INTRODUCTION: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies. METHODS: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described. RESULTS: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term--the originally reported finding--or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods. CONCLUSIONS: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists.

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Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study.

Publications

Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study.

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