Abstract 21361: Genetic Predisposing and Protective Effect of KCNE2 Variants in Atrial Fibrillation
Backgrounds: Recent studies suggest that genetic mutation of the rapid delayed rectifier potassium channel (I Kr) may underlie atrial fibrillation (AF). We hypothesized that the single nucleotide polymorphisms (SNPs) of KCNE1 , KCNE2, and KCNH2 (HERG) genes associated with this channel may be related to the susceptibility of atrial fibrillation.
Methods: We carried out a case-control study to investigate how genetic variations in the KCNE1, KCNE2, and KCNH2 gene are associated with AF in Koreans. We examined a sample of 625 Koreans, comprising of 286 patients with AF who had no structural heart disease and preserved left ventricular function, and 339 controls. We analyzed 8 taq SNPs of KCNE1, 4 tag SNPs of KCNE2 , 9 tag SNPs of HERG gene among AF patients, which were discovered using the direct DNA sequencing technique. All subjects were genotyped for these polymorphisms by single base primer extension assay using the SNaPShotTM assay. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiography and blood sample for genetic analysis were also obtained.
Results: We analyzed 8 taq SNPs in KCNE1 (−61557 A/G, 2851A/G, 2919 C/T, 2870 A/G, −62110A/C, 112 A/G, −109 T/C, 880 C/G), 4 taq SNPs in KCNE2 (−7187 T/C, −6362 A/G, −72 A/T, −56C/T), and 9 taq SNPs in KCNH2 (28804 C/T, 29468 A/C, 26213 G/A, −57 C/T, 3877 C/T, IVS3–34 A/G, IVS13+22 A/G, −867C/T) among the discovered SNPs. In single-locus analyses, no associations between SNPs and AF in KCNE1 and KCNH2 was observed. However, the recessive form of 72A/T in KCNE 2 was weak predisposing factor (OR, 0.61, 95% CI 0.39–0.99, p=0.04) and the dominant form of 56 C/T in KCNE 2 showed protective effect (OR, 2.8, 95% CI 1.19–6.76, p=0.018).
Conclusions: This study demonstrates the association of KCNE2 gene polymorphisms with nonfamilial AF. These data suggest that KCNE2 may contribute to the development of AF in Korean as predisposing or protecting effect. .
- © 2010 by American Heart Association, Inc.