Lack of genetic susceptibility in takotsubo cardiomyopathy: a case-control study
Emma Mattsson1, Peter Saliba-Gustafsson2, Ewa Ehrenborg2
1Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Sjukhusbacken 10, 11883, Stockholm, Sweden.
Insights
This study found no genetic link between Takotsubo cardiomyopathy (TCM) and the ADRB1, GRK5, or BAG3 genes. Further research is needed to identify the genetic factors contributing to this heart condition.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Takotsubo cardiomyopathy (TCM), or "broken heart syndrome," is a heart failure type with temporary ventricular dysfunction.
- Its exact pathophysiological mechanisms remain unknown, despite links to catecholamines and evidence of genetic predisposition.
- Previous small studies suggested associations with ADRB1, GRK5, and BAG3 genes, but consensus was lacking.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in the ADRB1, GRK5, and BAG3 genes and Takotsubo cardiomyopathy (TCM).
- To determine if these candidate genes contribute to the genetic predisposition of TCM.
- To clarify the genetic underpinnings of TCM by examining a large patient cohort.
Main Methods:
- Recruited 258 TCM patients and matched controls (164 with CAD, 243 without) from the Swedish Coronary Angiography and Angioplasty Register (SCAAR).
- Isolated DNA from saliva samples for genotyping of candidate SNPs in ADRB1, GRK5, and BAG3 genes.
- Compared allele frequencies and calculated Odds Ratios (OR) with 95% Confidence Intervals (CI) between TCM patients and controls.
Main Results:
- No significant differences in allele frequencies were observed between TCM patients and control groups.
- Odds Ratios (95% CI) for having at least one minor allele 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.
- These results indicate no association between the studied SNPs in ADRB1, GRK5, and BAG3 and TCM.
Conclusions:
- Genotyping a large Takotsubo cardiomyopathy cohort demonstrated a lack of association with candidate SNPs in ADRB1, GRK5, and BAG3 genes.
- The findings suggest these specific genes do not play a significant role in the development of TCM.
- Further research is required to identify novel genetic candidates that may contribute to the pathophysiology of Takotsubo cardiomyopathy.
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 β1-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.
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