TY - JOUR
T1 - Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology
AU - Bondue, Antoine
AU - Arbustini, Eloisa
AU - Bianco, Anna
AU - Ciccarelli, Michele
AU - Dawson, Dana
AU - De Rosa, Matteo
AU - Hamdani, Nazha
AU - Hilfiker-Kleiner, Denise
AU - Meder, Benjamin
AU - Leite-Moreira, Adelino F.
AU - Thum, Thomas
AU - Tocchetti, Carlo G.
AU - Varricchi, Gilda
AU - Van der Velden, Jolanda
AU - Walsh, Roddy
AU - Heymans, Stephane
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Dilated Cardiomyopathy
KW - Genetics
KW - Genome-environment interaction
KW - ANTHRACYCLINE-INDUCED CARDIOTOXICITY
KW - GENOME-WIDE ASSOCIATION
KW - DOXORUBICIN-INDUCED CARDIOMYOPATHY
KW - RIGHT-VENTRICULAR CARDIOMYOPATHY
KW - CONGESTIVE-HEART-FAILURE
KW - MYOSIN HEAVY-CHAIN
KW - A/C GENE-MUTATIONS
KW - MOGE(S) CLASSIFICATION
KW - HYPERTROPHIC CARDIOMYOPATHY
KW - PERIPARTUM CARDIOMYOPATHY
U2 - 10.1093/cvr/cvy122
DO - 10.1093/cvr/cvy122
M3 - Article
SN - 0008-6363
VL - 114
SP - 1287
EP - 1303
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 10
ER -