Susceptibility genes and modifiers for cardiac arrhythmias.

The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The marked clinical heterogeneity known from these familial arrhythmia syndromes has led to the development of a multifactorial ("multi-hit") concept of arrhythmogenesis in which causal gene mutations have a major effect on disease expression that is further modified by other factors such as age, gender, sympathetic tone, and environmental triggers. Systematic genetic studies have unraveled an unexpected DNA sequence variance in these arrhythmia genes that has ethnic-specific patterns. Whether this genetic variance may contribute as a second genetic modifier for arrhythmia development is under current investigation. The aim of this article is to review common genetic variation in ion channel genes and to compare these recent findings.