Browse > Article
http://dx.doi.org/10.5808/GI.2012.10.2.110

Genetic Analysis of SCN5A in Korean Patients Associated with Atrioventricular Conduction Block  

Park, Hyoung-Seob (Division of Cardiology, Department of Internal Medicine, Keimyung University School of Medicine)
Kim, Yoon-Nyun (Division of Cardiology, Department of Internal Medicine, Keimyung University School of Medicine)
Lee, Young-Soo (Department of Internal Medicine, Catholic University Medical Center)
Jung, Byung-Chun (Department of Internal Medicine, Daegu Fatima Hospital)
Lee, Sang-Hee (Department of Internal Medicine, Yeungnam University College of Medicine)
Shin, Dong-Gu (Department of Internal Medicine, Yeungnam University College of Medicine)
Cho, Yong-Keun (Department of Internal Medicine, Kyungpook National University Hosital)
Bae, Myung-Hwan (Department of Internal Medicine, Kyungpook National University Hosital)
Han, Sang-Mi (D&P Biotech)
Lee, Myung-Hoon (D&P Biotech)
Publication Information
Genomics & Informatics / v.10, no.2, 2012 , pp. 110-116 More about this Journal
Abstract
Recent several studies have shown that the genetic variation of SCN5A is related with atrioventricular conduction block (AVB); no study has yet been published in Koreans. Therefore, to determine the AVB-associated genetic variation in Korean patients, we investigated the genetic variation of SCN5A in Korean patients with AVB and compared with normal control subjects. We enrolled 113 patients with AVB and 80 normal controls with no cardiac symptoms. DNA was isolated from the peripheral blood, and all exons (exon 2-exon 28) except the untranslated region and exon-intron boundaries of the SCN5A gene were amplified by multiplex PCR and directly sequenced using an ABI PRISM 3100 Genetic Analyzer. When a variation was discovered in genomic DNA from AVB patients, we confirmed whether the same variation existed in the control genomic DNA. In the present study, a total of 7 genetic variations were detected in 113 AVB patients. Of the 7 variations, 5 (G87A-A29A, intervening sequence 9-3C>A, A1673G-H558R, G3578A-R1193Q, and T5457C-D1819D) have been reported in previous studies, and 2 (C48G-F16L and G3048A-T1016T) were novel variations that have not been reported. The 2 newly discovered variations were not found in the 80 normal controls. In addition, G298S, G514C, P1008S, G1406R, and D1595N, identified in other ethnic populations, were not detected in this study. We found 2 novel genetic variations in the SCN5A gene in Korean patients with AVB. However, further functional study might be needed.
Keywords
atrioventricular block; Korean; multiplex polymerase chain reaction; sodium channel protein type 5 subunit alpha;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Takahata T, Yasui-Furukori N, Sasaki S, Igarashi T, Okumura K, Munakata A, et al. Nucleotide changes in the translated region of SCN5A from Japanese patients with Brugada syndrome and control subjects. Life Sci 2003;72:2391-2399.   DOI   ScienceOn
2 Ye B, Valdivia CR, Ackerman MJ, Makielski JC. A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation. Physiol Genomics 2003;12:187-193.   DOI
3 Viswanathan PC, Benson DW, Balser JR. A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. J Clin Invest 2003;111:341-346.   DOI
4 Sun A, Xu L, Wang S, Wang K, Huang W, Wang Y, et al. SCN5A R1193Q polymorphism associated with progressive cardiac conduction defects and long QT syndrome in a Chinese family. J Med Genet 2008;45:127-128.
5 Hwang HW, Chen JJ, Lin YJ, Shieh RC, Lee MT, Hung SI, et al. R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese. J Med Genet 2005;42:e7.   DOI
6 Tan HL, Bezzina CR, Smits JP, Verkerk AO, Wilde AA. Genetic control of sodium channel function. Cardiovasc Res 2003;57:961-973.   DOI   ScienceOn
7 Schott JJ, Alshinawi C, Kyndt F, Probst V, Hoorntje TM, Hulsbeek M, et al. Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999;23:20-21.
8 McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, National Center for Biotechnology Information, National Library of Medicine. Bethesda, MD: Online Mendelian Inheritance in Man, OMIM. Accessed 2001 Dec 5. Available from: http://www.ncbi.nlm.nih.gov/omim/.
9 Brink PA, Ferreira A, Moolman JC, Weymar HW, van der Merwe PL, Corfield VA. Gene for progressive familial heart block type I maps to chromosome 19q13. Circulation 1995;91:1633-1640.   DOI   ScienceOn
10 Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, et al. Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A 1992;89:554-558.   DOI   ScienceOn
11 Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC, et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation 2002;105:1943-1948.   DOI   ScienceOn
12 Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, van Tintelen PJ, et al. A sodium-channel mutation causes isolated cardiac conduction disease. Nature 2001;409:1043-1047.   DOI   ScienceOn
13 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.   DOI   ScienceOn
14 Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, et al. Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. Am J Med Genet 1999;86:470-476.   DOI   ScienceOn
15 Wang DW, Viswanathan PC, Balser JR, George AL Jr, Benson DW. Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation 2002;105:341-346.   DOI   ScienceOn
16 Hu D, Barajas-Martinez H, Nesterenko VV, Pfeiffer R, Guerchicoff A, Cordeiro JM, et al. Dual variation in SCN5A and CACNB2b underlies the development of cardiac conduction disease without Brugada syndrome. Pacing Clin Electrophysiol 2010;33:274-285.   DOI   ScienceOn
17 Kyndt F, Probst V, Potet F, Demolombe S, Chevallier JC, Baro I, et al. Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation 2001;104:3081-3086.   DOI   ScienceOn
18 Chen JZ, Xie XD, Wang XX, Tao M, Shang YP, Guo XG. Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their relation with Brugada syndrome. Chin Med J (Engl) 2004;117:652-656.
19 Shin DJ, Jang Y, Park HY, Lee JE, Yang K, Kim E, et al. Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome. J Hum Genet 2004;49:573-578.   DOI   ScienceOn
20 Grant AO. Molecular biology of sodium channels and their role in cardiac arrhythmias. Am J Med 2001;110:296-305.   DOI   ScienceOn
21 Shin CH, Kim NH, Kim KH, Yoo SS, Choi YB, Oh SK, et al. A family with a missense mutation in the SCN5A gene. Korean Circ J 2003;33:150-154.