Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review

Abstract

Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or as left ventricular apical balloon syndrome in recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the limited understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in recent years, and particularly correlated to the SARS-CoV-2 pandemic, leads us to the imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and of targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial forms of TTS have been described. However, a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we here conducted a systematic review of the literature before June 2021, to contribute to the identification of potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but few in number and with diverse limitations. Consequently, we concluded that further work is needed to address the gaps discussed, and clear evidence may arrive by using multi-omics investigations.

The Octopus Trap of Takotsubo and Stroke: Genetics, Biomarkers and Clinical Management

“…Two principal studies focused on adrenergic receptor and ESR genes [ 3 ], encoding for the main proteins involved in physiological cardiac function, although conflicting results did not lead to a well-defined picture of the TC pathophysiology. Interestingly, a very recent systematic review has been performed to cast light on the potential genetic and epigenetic factors significantly associated with TC [ 80 ]. The data obtained suggested that genetic variants of ADRB1, GRK5, and BAG3 genes, or variants of APOE, MFGE8, ALB, APOB, SAA1, A2M, and C3 genes, can probably interact with the environment and emotional/physical stress and predispose certain subjects more than others to develop TC.…”

An update on takotsubo syndrome

“…Other factors TTS may have genetic influences, identified by a limited number of case studies. 33 These studies found TTS to be apparent amongst siblings and parent-child participants. There is a need for larger studies as case study findings may not represent the whole TTS population.…”

“…TTS may have genetic influences, identified by a limited number of case studies 33 . These studies found TTS to be apparent amongst siblings and parent-child participants.…”

Takotsubo Syndrome: Translational Implications and Pathomechanisms

“…Currently, a genetic predisposition has been suggested based on several familial TTS cases [124][125][126]. Furthermore, most postmenopausal women experience acute stressful events, but only a small percentage of them will develop TTS.…”