Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

Antoine Bondue, Eloisa Arbustini, Anna M Bianco, Michele Ciccarelli, Dana Dawson, Matteo De Rosa, Nazha Hamdani, Denise Hilfiker-Kleiner, Benjamin Meder, Adelino Leite Moreira, Thomas Thum, Carlo Gabriele Tocchetti, Gilda Varricchi, Jolanda Van der Velden, Roddy Walsh, Stephane Heymans

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Abstract

Dilated cardiomyopathy (DCM) frequently affects relatively young, economically and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance -malignancy of the mutated gene- but also on epigenetics, age, toxic factors, pregnancy and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN) or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart.

Original languageEnglish
Pages (from-to)1287-1303
Number of pages18
JournalCardiovascular Research
Volume114
Issue number10
Early online date23 May 2018
DOIs
Publication statusPublished - 1 Aug 2018

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Keywords

  • Journal Article
  • dilated cardiomyopathy
  • genetics
  • genome-environment interaction

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