ABSTRACT: The purpose of this study was to investigate the association of the polymorphisms of the KCNE1 gene with atrial fibrillation (AF) in a Chinese Han population.Three hundred seven AF patients and 330 age- and sex-matched controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method for two single-nucleotide polymorphisms (rs1805127 and rs1892593) of the human KCNE1 gene.The frequencies of the AA, AG, and GG genotypes of rs1805127 were 11.7%, 50.0%, and 43.3%, respectively, in the AF group, whereas the ones in the control group had frequencies of 19.4%, 44.9%, and 35.8%, respectively. There were significant differences in frequencies of these three genotypes (?(2)=7.820, p=0.016) and G allele (65.8% vs. 58.2%; ?(2)=8.266, p=0.005). The frequencies of AA, AG, and GG of rs1892593 were 38.4%, 47.9%, and 13.7% in the AF group, whereas the ones in the control group had frequencies of 37.8%, 48.5%, and 14.0%, respectively. There was no difference in distributions of frequencies of these three genotypes and allele (?(2)=0.051, p=0.978; ?(2)=1.024, p=0.837, respectively) between AF patients and control subjects. We also found that rs1805127 was associated with left atrial diameter and left ventricular end diastolic diameter in AF patients (?(2)=24.883, p<0.001; ?(2)=34.901, p<0.001, respectively). Logistic regression analysis showed that rs1805127 was an independent risk factor of AF in a Chinese Han population (odds ratio [OR]=1.66, 95% confidence interval [CI]: 1.02-2.68 for AG; OR=2.03, 95% CI: 1.24-3.31 for GG).The genetic polymorphism of KCNE1 was associated with increased risk of AF in a Chinese Han population.