Manjit Singh Oration 2017 / Cardiomyopathy: genetic and evolutionary perspectives

K. Thangaraj
Centre for Cellular and Molecular Biology, Uppal Road Hyderabad, India

Cardiomyopathy due to sarcomeric gene mutations is a major cause for heart failure. However, its genetic etiology remains largely unknown, particularly in Indian subcontinent. Therefore, we have analysed sarcomeric genes, including; MYBPC3, TNNT2, TNNI3, TPM1 and MYH7 in dilated (DCM) and hypertropic cardiomypathy (HCM). We found a 25 bp deletion in the MYBPC3 that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (OR = 6.99 (3.68– 13.57), P = 4 X 10-11) and that disrupts cardiomyocyte structure in vitro. We have also screened for this mutation in different ethnic populations, who are inhabiting all the continent and found its prevalence was high (~ 4%) in populations of Indian subcontinent. We further estimated that more than 55 million people are at risk worldwide, almost 1% of the world’s population. Whereas, other mutations are either in low frequency or private, affection only single family. Apart from sarcomeric genes, we discovered rare, functional RAF1 mutations in 3 cohorts (South Indian, North Indian and Japanese). Remarkably, we found these mutations only in childhood-onset DCM. Detailed genetic study and why the frequencies of disease causing variations are different in India would be discussed at the time of presentation.