Genetic polymorphisms and arrhythmia susceptibility.

Over the past 10 years, remarkable advances have been made in identifying the genes responsible for primary electrical heart diseases, such as congenital long QT syndrome and Brugada syndrome. Basic and clinical studies on these inherited arrhythmias have provided significant insight into the molecular basis of cardiac electrophysiology and the mechanisms of arrhythmias. However, many studies of genotype - phenotype relationships in these diseases have revealed considerable phenotypic variability in individuals from the same kindred carrying the identical disease-associated DNA variant, as is commonly observed in other polygenic disorders. Furthermore, despite rapid progress in understanding the molecular basis of primary electrical heart diseases, there is little insight into the genetics of acquired arrhythmias. Recently, it has been recognized that common genetic polymorphisms in cardiac ion channel and other genes may modify cardiac excitability, which in turn predisposes affected individuals to arrhythmias in the presence of triggering factors, such as electrolyte abnormalities or drugs. This paper reviews the current understanding of the contribution of genetic polymorphisms to the pathophysiology of cardiac arrhythmias.