Atrial Fibrillation Genetic Considerations: The Basic Scientist's Perspective

Common atrial fibrillation (AF) is a complex disease, and its pathogenesis involves multiple genetic factors, environmental factors, and interactions among these factors. Genetic factors clearly contribute to the risk of common AF. Parental AF increases by more than threefold the risk of AF under age of 75 years in offspring, and first-degree relatives have almost fivefold more risk of developing AF before the age of 60 years. Candidate gene case—control studies investigated the roles of several genes in common AF and thromboembolism in AF, including KCNE1, KCNE4, KCNE5, GNB3, AGT, CETP, coagulation factor II, α-fibrinogen, factor XIII, and IL6. Genomewide single nucleotide polymorphism association studies is the state-of-the art study design for dissecting the common complex AF trait and have successfully identified two SNPs on chromosome 4q25 that are associ ated with risk of atrial fibrillation. Rare families with AF have been reported, and studies of these families identified mutations in several genes for AF, including KCNQ1, KCNE2, KCNE3, and KCNJ2. Two autosomal dominant AF genes were mapped to chromosome 10 q and 6 q, and one autosomal recessive gene for AF was mapped to 5 p, but these genes have not yet been identified. Also, AF can occur in patients with dilated cardiomyopathy with SCN5A and LMNA mutations, long QT syndrome patients with an ankyrin-B mutation, and short QT syndrome patients with a KCNH2 mutation. Genetic studies of AF will continue to provide insight into molecular mechanisms for the pathogenesis of AF and will facilitate realization of genetic testing and genotype-based therapies (personalized medicine) for AF patients.