Recent studies suggest that genetic mutation of the slow delayed rectifier potassium channel (IKs) 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.

Keywords:
Atrial fibrillation, Slow delayed rectifier K+ channel, Single nucleic polymorphism, KCNQ1, KCNE4
1.
Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, Jin HW, Sun H, Su XY, Zhuang QN, Yang YQ, Li YB, Liu Y, Xu HJ, Li XF, Ma N, Mou CP, Chen Z, Barhanin J, Huang W: KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003;299:251–254.
2.
Lai LP, Su MJ, Yeh HM, Lin JL, Chiang FT, Hwang JJ, Hsu KL, Tseng CD, Lien WP, Tseng YZ, Huang SK: Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation. Am Heart J 2002;144:485–490.
3.
Moe GK, Abildskov JA: Atrial fibrillation as a self-sustaining arrhythmia independent of focal discharge. Am Heart J 1959;58:59–70.
4.
Nattel S, Liu L, St-Georges D: Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties. Cardiovasc Res 1998;37:627–635.
5.
Teng S, Ma L, Zhen Y, et al: Novel gene hKCNE4 slows the activation of the KCNQ1 channel. Biochem Biophys Res Commun 2003;303:808–813.
6.
Iwasa H, Itoh T, Nagai R, Nakamura Y, Tanaka T: Twenty single nucleotide polymorphisms (SNPs) and their allelic frequencies in four genes that are responsible for familial long QT syndrome in the Japanese population. J Hum Genet 2000;45:182–183.
7.
Ackerman MJ, Tester DJ, Jones GS, Will ML, Burrow CR, Curran ME: Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. Mayo Clin Proc 2003;78:1479–1487.
8.
Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000;102:1178–1185.
9.
Westenskow P, Splawski I, Timothy KW, Keating MT, Sanguinetti MC: Compound mutations: a common cause of severe long-QT syndrome. Circulation 2004;109:1834–1841.
10.
Sharma D, Glatter KA, Timofeyev V, Tuteja D, Zhang Z, Rodriguez J, Tester DJ, Low R, Scheinman MM, Ackerman MJ, Chiamvimonvat N: Characterization of a KCNQ1/KVLQT1 polymorphism in Asian families with LQT2: implications for genetic testing. J Mol Cell Cardiol 2004;37:79–89.
11.
Kubota T, Horie M, Takano M, Yoshida H, Takenaka K, Watanabe E, Tsuchiya T, Otani H, Sasayama S: Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias. J Cardiovasc Electrophysiol 2001;12:1223–1229.
12.
Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y: Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation. Am J Hum Genet 2004;75:899–905.
13.
Brugada R, Tapscott T, Czernuszewicz GZ, et al: Identification of a genetic locus for familial atrial fibrillation. N Engl J Med 1997;336:905–911.
14.
Ellinor PT, Shin JT, Moore RK, et al: Locus for atrial fibrillation maps to chromosome 6q14–16. Circulation 2003;107:2880–2883.
15.
Tsai CT, Lai LP, Lin JL, et al: Renin-angiotensin system gene polymorphisms and atrial fibrillation. Circulation 2004;109:1640–1646.
© 2007 S. Karger AG, Basel
2006
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