In this new study, researchers from the Wellcome Sanger Institute, the University of Cambridge, the Massachussetts Institute of Technology, Lund University, and Health in Code have developed a new computational model that allows understanding the correlation between the clinical expression of cardiomyopathies and genetic alterations of the troponin complex.
The research was published on 14 June 2021 in the journal npj Genomic Medicine and allowed confirming that some genetic alterations and hot spots are associated with different hereditary diseases that affect cardiac muscle function.
Among the cardiac diseases associated with genetic variants, the most common ones are inherited cardiomyopathies, which affect approximately 2% of the global population.
Cardiomyopathies encompass a group of cardiac muscle diseases that affect the structure and physiological functions of the myocardium. The majority of genetic variants appear in sarcomeric proteins, with variations in the troponin complex (T, I, and C troponins) accounting for 8-10% of these cases.
Different variants in different specific locations of the genes encoding these proteins have been found to be associated with different cardiomyopathy types, leading to different prognoses.
First, the most relevant regions of troponin were identified based on their interaction and on computational models, in order to later identify critical variation sites. Once all this information was gathered, a meta-analysis of the clinical data from the literature and from public databases was performed to establish a prognosis for each of the regions, establishing a genotype-phenotype correlation.
As Professor Mark Caulfield states, this new tool is a step forward with a huge potential in precision cardiology, which will benefit patients who present with some hereditary cardiac disease associated with these genetic defects.
Shakur R, Ochoa JP, Robinson AJ, Niroula A, Chandran A, Rahman T, et al. Prognostic implications of troponin T variations in inherited cardiomyopathies using systems biology. npj Genomic Med. 2021;6(1):1–11.