An mRNA signature has been uncovered that predicts hypertrophic cardiomyopathy, according to new research from the Nantong University in China. Their study used sequencing data and machine learning to find the signature, which includes FCN3, MYH6, and RASD1.
Early detection of Hypertrophic cardiomyopathy (HCM) is important because this condition can lead to cardiac dysfunction and sudden death. HCM is a genetic heterogeneous disorder associated with mutations in certain genes.
This team set out to develop a HCM signature using bioinformatics and machine learning methods. They used HCM and normal tissue data obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. DEGs were mainly enriched in immune and inflammatory response pathways. Past findings, the researchers noted, have found the presence of mild systemic and local inflammation in individuals with HCM.
Next the team used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to perform enrichment analysis of HCM-associated DEG and determine Hub genes for HCM. Hub genes interact with many other genes and play a critical role in biological processes and gene regulation.
The team then used a zebrafish model to simulate changes in the hub genes in the HCM and to observe effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and they screened 157 DEGs.
Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM.
Although the etiology of cardiovascular disease is varied, heart failure is commonly the final stage. Noticeably, pathological cardiac hypertrophy could easily develop into heart failure and therefore becomes an increasingly important cause of cardiovascular diseases.
Cardiovascular myocardial hypertrophy causes a variety of major cardiovascular diseases. Cardiomyocyte enlargement leads to myocardial hypoxia and cardiac remodeling due to excessive capillary supply. If without timely intervention, the heart will further develop into an irreversible decompensation period, accompanied by cardiac dysfunction, ultimately leading to heart failure and death.
Gene sequencing has made it possible to diagnose HCM patients with a family history and in asymptomatic patients to avoid sudden death. The European and American Guidelines encourage the use of genetic testing for potential HCM patients.
