Genetics of atrial fibrillation: rare mutations, common variants and clinical relevance?].

M F Sinner, A Pfeufer, S Kääb

GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Humangenetik.

Herzschrittmachertherapie & Elektrophysiologie 2006 Jun

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Atrial fibrillation (AF) is considered the, by far, the most common arrhythmia of man, affecting millions of patients worldwide. The high socio-economic relevance is due to several severe complications and therefore requires profound scientific research in the field of etiology and treatment options. Atrial fibrillation typically occurs in the older patient who often suffers from a number of underlying diseases that act as predisposing factors. That genetics contribute strongly to this rhythm disorder is therefore not evident at a first glance. However, there are a number of investigations that prove familial accumulation for lone AF. Furthermore it is remarkable that many older patients suddenly develop atrial fibrillation without underlying disease, while others remain in sinus rhythm although suffering from a series of risk factors. Considering all this, genetic interference becomes most probable. Therefore in the recent past remarkable endeavours have been ventured to clarify the genetic basis of both lone AF and AF in the context of underlying diseases. For the former, until now four different genetic loci and three disease genes have been identified as causative. Concerning AF in the general population, mainly studies turning the spotlight on single-nucleotide polymorphisms (SNPs) have been applied. It is assumed that SNPs in disease-causing genes are distributed differentially among healthy and diseased individuals. These differences in frequency have been investigated with case-control studies. Up to now six different genes have been found to be associated with AF, including the genes for angiotensin-converting enzyme, angiotensinogen and several cardiac ion channels. Promising new technologies, especially high-throughput SNP genotyping and the genome wide scan for new candidate genes using chip arrays capable of genotyping up to 500 000 SNPs at a time, will multiply the speed to achieve new results. With that the possibility, approaches to optimize existing therapies and to open up new pathways to treat AF.

Citation

M F Sinner, A Pfeufer, S Kääb. Genetics of atrial fibrillation: rare mutations, common variants and clinical relevance?]. Herzschrittmachertherapie & Elektrophysiologie. 2006 Jun;17(2):95-105