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Front Physiol. 2016 Oct 28;7:499. eCollection 2016.

Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants.

Author information

1
Department of Internal Medicine, Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Sciences, University of Cincinnati College of Medicine Cincinnati, OH, USA.
2
AstraZeneca R&D Mölndal, Innovative Medicines and Early Development, Cardiovascular and Metabolic Diseases iMedMölndal, Sweden; Integrated Cardio Metabolic Centre, Karolinska Institutet, Myocardial Genetics, Karolinska University Hospital in HuddingeHuddinge, Sweden.

Abstract

The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM) is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. The South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM.

KEYWORDS:

MYH7; MYPBC3; South Asians; cardiac myosin binding protein-C; hypertrophic cardiomyopathy; β-myosin heavy chain

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