Molecular genetics of atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. There is genetic predisposition for the development of AF. Recently, by linkage analysis, several loci have been mapped for monogenetic AF, including 11p15.5, 21q22, 17q, 7q35-36, 5p13, 6q14-16, and 10q22. Some of these loci encode for subunits of potassium channels (KCNQ1, KCNE2, KCNJ2, and KCNH2 genes), and the remaining are yet unidentified. All of the known mutations are associated with a gain of function of repolarization potassium currents, resulting in a shortening of action potential duration and atrial refractory period, which facilitate multiple re-entrant circuits in AF. In addition to familial AF, common AF often occurs in association with acquired diseases such as hypertension, valvular heart disease, and heart failure. By genetic association study, some genetic variants or polymorphisms related to the mechanism of AF have been found to be associated with common AF, including genes encoding for subunits of potassium or sodium channels, sarcolipin gene, renin-angiotensin system gene, connexin-40 gene, endothelial nitric oxide synthase gene, and interleukin-10 gene. These observations suggest that genes related to ionic channels, calcium handling protein, fibrosis, conduction and inflammation play important roles in the pathogenesis of common AF. The complete elucidation of genetic loci for common AF is still in its infancy. However, the availability of genomewide scans with hundreds or thousands of polymorphisms has made it possible. However, challenges and pitfalls exist in association studies, and consideration of particular features of study design is necessary before making definite conclusions from these studies.
Tsai
Chia-Ti
CT
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Lai
Ling-Ping
LP
Hwang
Juey-Jen
JJ
Lin
Jiunn-Lee
JL
Chiang
Fu-Tien
FT
D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics
D015221:Potassium Channels; D015222:Sodium Channels