CCMB researchers reveal genetic mutations responsible for high mortality of cardiovascular diseases

Researchers at the Centre for Cellular and Molecular Biology (CCMB), Hyderabad have discovered some novel genetic mutations among Indians that are responsible for causing dilated cardiomyopathy, a condition attributed to the high mortality rate in the country due to cardiovascular diseases when compared to western countries.

Cardiomyopathy changes the integral structure of the heart muscle, and as a result, the organ is unable to pump blood efficiently. This increases the risk of heart failure leading to sudden cardiac death.

A team of CSIR-CCMB scientists led by Dr K Thangaraj have found novel genetic mutations in the beta myosin heavy chain gene (β-MYH7) that are responsible for causing dilated cardiomyopathy among Indians. The findings were published in the Canadian Journal of Cardiology - Open last week.

“The β-MYH7 is one of the major genes responsible for cardiac diseases globally. However, not many genetic studies were carried out in the Indian context,” said Dr Thangaraj, study's senior author, and presently Director, Centre for DNA Fingerprinting and Diagnostics (CDFD).

The CCMB team 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 Indians.

The research revealed 27 variations, of which seven mutations (8.0 per cent) 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. Applying bioinformatics tools, these mutations were predicted to be pathogenic.

A missense mutation is a gene variation which causes replacement of original amino acids, Thangaraj told DH. "Subsequent study using homology models of β-MYH7, we for 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”, said Dr Deepa Selvi Rani, lead author of the study.

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.

“The study could aid in developing gene-editing methods that may rescue cardiac contractility of failing hearts among Indians with the novel mutations”, said Dr Vinay Kumar Nandicoori, director, CCMB.

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