Denaturing high-performance liquid chromatography screening for KvLQT1 gene variations in patients with atrial fibrillation

Background: A mutation in the KvLQT1 gene has been reported to be responsible for autosomal dominant hereditary atrial fibrillation (Af). It is not known whether mutations in this gene are also responsible for Af in common clinical practice. Methods: We enrolled 100 consecutive patients with Af, as well as 50 normal individuals without Af. Total cellular DNA was isolated from peripheral leukocytes. Polymerase chain reactions were performed to amplify the translated region of the KvLQT1 gene. Denaturing high-performance liquid chromatography was subsequently used to screen for the presence of heteroduplexes, and DNA sequencing was applied to these heteroduplexes. Results: Among the 100 patients with Af, we identified six single-nucleotide polymorphisms (SNPs), including three intronic SNPs (in introns 1, 12, and 13, respectively), two synonymous SNPs (C435 to T and G1638 to A) and one non-synonymous SNP (C1343 to G with amino acid change P448 to R). Two of the intronic SNPs were present in only one patient with Af (intron 1 and intron 12). The other four SNPs were more common and were also present in normal individuals. The incidences of heterozygocity of the four common SNPs were not significantly different between normal individuals and patients of Af, nor were the incidences significantly different between patients with lone Af and patients with Af associated with organic heart disease. Conclusion: KvLQT1 mutation was not found in 100 patients with Af. Although common SNPs were identified, their incidences were not significantly different among normal individuals, patients with lone Af and patients with organic Af.