Background:There is evidence showing that genetic factors contribute to the pathogenesis of atrial fibrillation (AF). However, the molecular genetic defects in most other patients with AF remain unclear. In this study, we evaluated 100 unrelated sporadic cases with AF and sequenced KCNE2 gene, coding for 棺-subunit of potassium channel involved in the background potassium current. Additionally, we investigated whether there is an association between KCNE2 gene variants for the development of AF. Methods: Serial patients(n=100) with lone atrial fibrillation were enrolled between June, 2006 and May, 2007. For every case, an age and gender matched control was selected from the same population (n = 194). Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Results: We identified a single missense mutation (R27C) of KCNE2 and were found in single patient. DNA sequence analysis also revealed five polymorphisms in the study subjects. The distribution of allele for the C58T polymorphism was found to be significantly associated with AF status (P=0.041). Logistic regression analysis indicated that the KCNE2 58T allele carriers were positively associated with AF in male subjects (OR for TT/CT, 1.335; 95% CI, 1.003-1.771, P=0.048). Conclusion: This study suggest that KCNE2 gene polymorphism may contribute to the positive genetic risk factor for the development of AF.