title: Genetic modifiers of cardiac arrhythmias.
abstract: Rhythmic contraction of a four-chambered mammalian heart is a highly coordinated process, requiring a functional conduction system. Both acquired and inherited forms of arrhythmia can be life threatening, and are major causes of mortality and morbidity in developed nations. Knowledge derived from human genetics and from studies of mouse genetic models has led to the discovery of multiple molecular defects responsible for arrhythmogenesis, including mutations in ion channels, cytoplasmic ion-channel-interacting proteins, gap-junction proteins, transcription factors and, most recently, a kinase subunit. However, phenotypic expression of a given mutation does not always appear to be uniform in human patients, implying a contribution from environmental factors and/or the presence of other genetic modifiers. Accumulating evidence suggests that 'multiple hits' affecting the interaction and integrity of multiple pathways might be responsible for many forms of arrhythmia.
authors.affiliation: Dept of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
authors.forename: Hai-Chien
authors.initials: HC
authors.lastname: Kuo
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000200:Action Potentials; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology*; D002135:Calcium-Binding Proteins / Q000235:genetics; D017630:Connexins / Q000235:genetics; D004562:Electrocardiography; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000503:physiopathology; D051605:Kv Channel-Interacting Proteins; D011494:Protein Kinases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D017630:Connexins; D007473:Ion Channels; C496752:KCNIP2 protein, human; D051605:Kv Channel-Interacting Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases