The genetics of sudden cardiac death.
Sudden cardiac death (SCD), a sudden pulseless condition due to cardiac arrhythmia, remains a major public health problem despite recent progress in the treatment and prevention of overall coronary heart disease. In this review, we examine the evidence for genetic susceptibility to SCD in order to provide biological insight into the pathogenesis of this devastating disease and to explore the potential for genetics to impact clinical management of SCD risk. Both candidate gene approaches and unbiased genome-wide scans have identified novel biological pathways contributing to SCD risk. Although risk stratification in the general population remains an elusive goal, several studies point to the potential utility of these common genetic variants in high-risk individuals. Finally, we highlight novel methodological approaches to deciphering the molecular mechanisms involved in arrhythmogenesis. Although further epidemiological and clinical applications research is needed, it is increasingly clear that genetic approaches are yielding important insights into SCD that may impact the public health burden imposed by SCD and its associated outcomes.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21209, USA. arking@jhmi.edu
Dan E
DE
Arking
Nona
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Sotoodehnia
D000818:Animals; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D012307:Risk Factors
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human