title: Developmental aspects of cardiac arrhythmogenesis.
abstract: The transcriptional regulation orchestrating the development of the heart is increasingly recognized to play an essential role in the regulation of ion channel and gap junction gene expression and consequently the proper generation and conduction of the cardiac electrical impulse. This has led to the realization that in some instances, abnormal cardiac electrical function and arrhythmias in the postnatal heart may stem from a developmental abnormality causing maintained (epigenetic) changes in gene regulation. The role of developmental genes in the regulation of cardiac electrical function is further underscored by recent genome-wide association studies that provide strong evidence that common genetic variation, at loci harbouring these genes, modulates electrocardiographic indices of conduction and repolarization and susceptibility to arrhythmia. Here we discuss recent findings and provide background insight into these complex mechanisms.
authors.affiliation: Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Alex V
authors.initials: AV
authors.lastname: Postma
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.forename: Connie R
authors.initials: CR
authors.lastname: Bezzina
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000196:embryology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D007473:Ion Channels; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C501600:IRX5 protein, human; C095552:NKX2-5 protein, human; C103172:T-box transcription factor 5