Vnitr Lek 2003, 49(9):768-772

[Molecular genetic aspects of arrhythmias].

T Novotný: Interní kardiologická klinika Lékarské fakulty MU a FN Brno.

The sequencing of human genome was completed in 2001. The position of particular DNA base is established-i.e. we know all "letters" in the "book" but we understand only limited number of "words" i. e. only limited number of genes was identified. And the human genome consists of about 30,000 genes from which through the mechanism of alternative RNA splicing more than 100,000 genes can be derived. All the genes of one individual form the genotype. The expression of genotype in particular environment forms the phenotype. What is not present in genotype can neither be present in phenotype. In the last decade a substantial progress was achieved in understanding of membrane processes mostly due to research of relatively rare inherited monogenous arrhythmic syndromes--first of all the long QT syndrome. It is caused by mutations in ion channel genes and it provides a model of arrhythmogenesis on molecular level. Ventricular arrhythmias are important cause of mortality in patients with cardiovascular diseases. New studies have provided strong evidence for familial sudden cardiac death (SCD) aggregation and therefore also genetic influence. Parental history of SCD increases the relative risk of SCD for offspring to 1.8. In the case of both maternal and paternal SCD events the risk for offspring is a remarkable 9.4. There are 3 pathways by which genetic variation may contribute to risk for SCD: 1. alterations in electrogenesis and conduction, 2. formation and stability of atherosclerotic plaque, thrombogenesis and ischemia within the coronary circulation, 3. control of myocardial excitability and vascular motorics. The main objective of both today and future research is identification of inheritable "molecular" risk factors of arrhythmias. Understanding of this level of pathophysiological processes will subsequently lead to new generation of both diagnostic and therapeutic methods.