The single nucleotide polymorphisms of I_Ks potassium channel genes and their association with atrial fibrillation in a Chinese population

Recent studies suggest that genetic mutation of the slow delayed rectifier potassium channel (I_Ks) may underlie atrial fibrillation (AF). We investigated the association between AF and the single nucleotide polymorphisms (SNPs) of genes KCNQ1, KCNE1 and KCNE4 associated with this channel. Common non-synonymous SNPs in KCNQ1 and KCNE1 known to be frequent in Asian people were selected and direct sequencing of KCNE4 was performed to identify possible SNPs. The AF group consisted of 142 hospitalized patients with AF, the community control group consisted of 120 subjects, and a ward control group consisted of 118 hospitalized patients without AF. Restriction fragment length polymorphism analysis was performed to determine the genotypes. The minor allele frequencies of P448R, R519H, G643S for KCNQ1 and G38S and D85N for KCNE1 in the AF group, the community control group and the ward control group were 9.9, 7.9, 9.3%; 0, 0, -; 4.3, 4.2, 1.7%; 28.4, 31.7, 29.7%; 0.7, 0.4%, -, respectively. There was no significant association between these SNPs and AF phenotype. There were eight SNPs in the whole length of KCNE4 plus 1,000 bases upstream of this gene including the non-synonymous SNP E145D. Logistical regression analysis revealed a difference in the distribution of KCNE4 E145D in the AF and the community control group (minor allele frequency was 34.0 versus 27.1% respectively, OR = 1.66, p = 0.044). We provided the frequencies of non-synonymous SNPs of KCNQ1 and KCNE1 in Chinese population; none of these SNPs was associated with AF. But KCNE4 E145D may be associated with the AF phenotype.