Hyderabad: A team of scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have found novel genetic mutations in the beta myosin heavy chain gene (β-MYH7) that are responsible for causing dilated cardiomyopathy among Indians.
The death rate due to cardiovascular diseases is very high in India compared to western countries. In severe cardiomyopathy, one of the cardiovascular diseases, heart failures are common. Cardiomyopathy changes the integral structure of the heart muscle and as a result, the heart is unable to pump blood efficiently. This increases the risk of heart failure leading to sudden congestive heart failure.
A CCMB team was led by Dr. K. Thangaraj. The finding has been published in the Canadian Journal of Cardiology.
The β-MYH7 is one of the major genes implicated in cardiorespiratory diseases globally. “However, not many genetic studies were carried out in Indian cardiomyopathy patients. Hence, we sequenced β-MYH7 gene of 137 dilated cardiomyopathy patients along with 167 ethnically matched healthy controls to identify the mutation(s), if any, that are associated with dilated cardiomyopathy in Indian patients,” said Dr. Thangaraj, senior author of the study and director of Centre for DNA Fingerprinting and Diagnostics (CDFD).
Dr. Deepa Selvi Rani, the lead author of the study, said, “Our study revealed 27 variations, of which seven mutations (8.0%) were novel and were detected exclusively in Indian dilated cardiomyopathy patients. These included four missense mutations, each altered evolutionarily conserved amino acids in the β-MYH7 protein and were predicted to be pathogenic by bioinformatics tools. A subsequent study using homology models of β-MYH7, for the first time, demonstrated how these mutations uniquely disrupt a critical network of non-bonding interactions at the molecular level and may contribute to the development of disease phenotype.”
Each protein molecule is made up of specific amino acids. Various interactions between the amino acid residues drive the 3D structure of the protein, which determines its function. One amino acid change at a critical site can change a protein structure dramatically and lead to disease pathogenicity.
Dr. Vinay Kumar Nandicoori, the director of CCMB, said the study can help in developing gene-editing methods that may rescue cardiac contractility of failing hearts among Indians with the novel mutations.