Gene Polymorphisms, Mutations and Epigenetics in Heart Failure

Heart Failure (HF) is a complex clinical syndrome characterized by compromised cardiac output that leads to inadequate blood supply failing to meet the requirements of the metabolizing tissues of the body. HF is a silent epidemic that affects ~2% of the general population in the western world and its prevalence is steadily increasing. Although survival has improved, high morbidity and mortality render HF the most devastating cardiovascular disorder with considerable financial burden on public health care. The phenotypic variability of HF syndrome reflects the complexity of the underlying genetic background of the disease, as well as the interindividual susceptibility to external triggers. Although acquired clinical conditions account for the majority of HF development, a proportion of HF cases are due to inherited pathological states comprising myocardial disorders, mitochondrial diseases, metabolic disorders and congenital heart defect syndromes. Among those, inherited forms of cardiomyopathies constitute “naturally-occurring” disease models that provide the opportunity for an in depth investigation of the genotype–phenotype relationships. Advances in technology permitting high-throughput whole genome genotyping and sequencing, have provided invaluable insights into the genetic architecture, disease evolution and therapeutic response. However, despite the enormous wealth of genetic information derived from those studies and their contribution towards the identification of disease-specific genetic variants in complex diseases such as HF, a considerable amount of genetic information related to heritability is missing. In this chapter, we will review knowledge regarding the underlying complex genetic architecture of both acquired and inherited forms of HF, the role of epigenetics as a significant modifier mechanism in disease susceptibility and phenotypic heterogeneity, as well as advances in the field of pharmacogenetics of HF.

Keywords: Cardiomyopathies, Chromatin remodelling, Congenital heart defects, DNA methylation, Epigenetics, Genetics, Genetic testing, Heart failure, Histone, MicroRNAs, Pharmacogenetics, Single nucleotide polymorphisms.