Although the recovery rate is high in TC, hemodynamic and respiratory support may be required and sometimes, unfortunately, death may result. A better understanding of the mechanisms underlying the disease can aid in targeted management and better survival. Identifying the role of genetic variants will help both to understand the abnormalities in signaling pathways in these patients and to inform new therapeutic targets. In another study thought to be effective in Takotsubo syndrome; although there is no evidence for specific genetic variants in GRK5 or bAR that play a role in an individual's susceptibility to TC, this has been proposed as an interesting hypothesis. Therefore, further exploration of alternative candidates in the proposed signaling pathways or non-candidate approaches such as genome-wide screening is recommended [12, 13].
It is usually seen in the postmenopausal period of women, after emotional or physical stress. They reported that the reason why it is frequently seen in the postmenopausal period is that it makes the heart sensitive to catecholamines in connection with the decrease in estrogen, and therefore systolic dysfunction may develop more easily in the left ventricle of the heart under stress. Although its physiopathology has not been clarified yet, increased catecholamine levels are thought to play an important role. In addition, enlarged myocardium, hypertension, chronic obstructive pulmonary disease, decreased estrogen level, small vessel disease, myocarditis, insufficiency of myocardial fatty acid metabolism have also been blamed. Symptoms and electrocardiogram (ECG) findings mimic acute coronary syndrome .
Sharkey et al. (2009) published their study in which they genotyped three adrenergic receptor polymorphisms in a cohort of 41 patients with stress cardiomyopathy (SK). Also known as takotsubo cardiomyopathy and apical balloon syndrome, this idiopathic but reversible disorder was typically seen in postmenopausal women. It was also manifested by ischemia-like chest pain, transient ECG changes, and minor cardiac biomarker elevation after acute emotional or physical stress. Coronary arteries were not occluded in angiography of Takotsubo patients. Sharkey et al. investigated functional polymorphisms of B1 and alpha 2c adrenergic receptors. Despite the increased activation of the sympathetic nervous system, in which catecholamines increase (epinephrine, norepinephrine, dopamine) and this elevation stimulates adrenergic receptors, it has been reported that there is no significant difference between Takotsubo patients and female controls when the polymorphism frequencies are compared . This result was similar our research results.
Figtree et al. (2013) examined the potential association of genetic variants in the adrenergic and estrogen signaling pathways with TC in a large cohort of 92 Takotsubo patients recruited from four major Australian centers. While genotypic variation is an attractive way to explain disease susceptibility, this study demonstrates that major candidate polymorphisms in adrenergic, estrogen, and GRK5 signaling pathways genes are not associated with TC .
Studies have led to the hypothesis that epinephrine is the main circulating catecholamine under stress, leading to the hypothesis that regional differences in epinephrine-sensitive B2 receptors may explain the myocardial response to the catecholamine surge seen in Takotsubo Cardiomyopathy . Therefore, it has been hypothesized that its mutation in adrenergic receptors may increase the sensitivity of the heart to adrenergic stress. In polymorphism studies with primers designed for the ADRB1 and ADRB2 genes, comprehensive DNA sequencing of these adrenergic receptor genes did not reveal any mutations in the familial Takotsubo Cardiomyopathy case. While a molecular defect in adrenergic signaling remains a plausible pathogenic mechanism, our data, along with the findings of Sharkey et al., suggest that Takotsubo Cardiomyopathy is probably not based on genetic variation in adrenergic receptors [17, 18].
Eitel et al. (2017), in a large GWAS study; It has been concluded that the genes in the ± 500kb upstream and downstream regions of the SNPs in the gene regions that are thought to cause TC may be associated with different cancer types, obesity and heart rate variability, but cannot be directly responsible for TC. According to these results; although there is a familial predisposition for TC in several families, or studies have been conducted in postmenopausal women; it has been reported that larger-scale TC cohorts should be established .
In a study in rats; Expression of β-1AR and β-2AR mRNA in Dilated Cardiomyopathies treated with doxoribucin was evaluated by RT-qPCR and reported no change in β-1AR and β-2AR gene expressions .
Although a few familial cases of Takotsubo have been reported, no responsible gene mutation, variation or polymorphism has been clearly identified so far, so the genetic causes underlying TC have not yet been clearly elucidated.