Table 1.

Mechanistic subclassification of lone atrial fibrillation and putative pharmacogenetic strategy (modified from reference 9).

AF Subclassification	Culprit Gene(s)	Functional Effect
Enhanced atrial action potential repolarization	KCNQ1 KCNE2 KCNJ2 KCNE5	Enhanced slow component of the delayed rectifier potassium current (IKs) Enhanced KCNQ1-KCNE2 potassium current Enhanced inward rectifier current (IK1) Enhanced IKs
Delayed atrial action potential repolarization	KCNA5 SCN5A	Decreased ultra-rapid component of the delayed rectifier potassium current (Ikur) Hyperpolarizing shift in Nav1.5 inactivation
Conduction velocity heterogeneity	GJA5 GJA1	Heterogeneous reduction in gap junction conduction
Cellular hyperexcitability	SCN5A	Depolarizing shift in Nav1.5 inactivation
Hormonal modulation of atrial electrophysiology	NPPA	Increased circulating levels of mutant ANP
Cholinergic	Unknown	Enhanced cholinergic sensitivity