Paper - WANFANG MED ONLINE

You Position: Home > Paper

Single nucleotide polymorphisms of the SCN5A gene in Han Chinese and their relation with Brugada syndrome

( views:196, downloads:8 )

Author:: No author available

Journal Title:: CHINESE MEDICAL JOURNAL

Issue:: 5

DOI:: No doi available

Key Word:: polymorphism,genetics;SCN5A gene;Brugada syndrome;arrhythmia

Abstract： Background Mutations in the cardiac sodium channel gene (SCN5A) may lead to a broad spectrum of familial arrhythmias, including long QT syndrome (LQTS), idiopathic ventricular fibrillation (IVF), and isolated cardiac conduction diseases. Recent studies have shown that polymorphisms in the SCN5A gene also play an important role in the manifestation of disorders involving cardiac excitability. In this study, we investigated the polymorphisms of the SCN5A gene in Han Chinese and its relation to Brugada syndrome (BS).Methods Genomic DNA was isolated from 120 unrelated healthy volunteers and 48 unrelated Brugada syndrome patients by means of standard procedures. All exons including the putative splicing sites of the SCN5A gene were amplified by PCR and sequenced directly or after subcloning using an ABI Prism 377 DNA sequencer. Results A total of 5 single nucleotide polymorphisms (SNPs) were identified in the Han Chinese population, including 3 novel ones: G87A(A29A), 4245+82A>G, and G6174A. The allele frequencies of each SNP in the Han Chinese population were as follows: G87A (A29A) 27.5%, A1673G (H558R) 10.4%, 4245+82A>G 32.8%, C5457T (D1819D) 41.3%, and G6174A 44.9%. S1102Y and 10 other SNPs identified in other ethnic populations were not detected in this study. There was no significant difference in the allele frequency of A1673G (H558R) between different ethnic populations (all P>0.5). On the other hand, the allele frequency of C5457T (D1819D) among Han Chinese was similar to its frequency among Japanese (P>0.5), but higher than that among Americans (P<0.005). The allele G1673 (R558) was over-represented in BS patients compared to controls (P<0.005), but there was no significant difference in genotype frequencies at this locus. There were also no differences in either the allele or genotype frequencies of the 4 other identified SNPs when comparing BS patients with healthy controls. Conclusions The distribution of SCN5A SNPs may vary between different ethnicities. The polymorphism of A1673G might be associated with BS and may contribute to a susceptibility to BS in Han Chinese.

Reference

[1]G Q, Daley,M, Cargill.The heart SNPs a beat: polymorphisms in candidate genes for cardiovascular disease.[J].2001,11(2).
[2]Q, Chen,G E, Kirsch,D, Zhang,etc.Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.[J].1998,392(6673).
[3]Qing Wang,Jiaxiang Shen,Igor Splawski,etc.SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome[J].1995,80(5).
[4]H L, Tan,M T, Bink-Boelkens,C R, Bezzina,etc.A sodium-channel mutation causes isolated cardiac conduction disease.[J].2001,409(6823).
[5]Qing Wang,Zhizhong Li,Jiaxiang Shen,etc.Genomic Organization of the HumanSCN5AGene Encoding the Cardiac Sodium Channel[J].1996,34(1).
[6]Geoffrey W Abbott,Federico Sesti,Igor Splawski,etc.MiRP1 Forms IKr Potassium Channels with HERG and Is Associated with Cardiac Arrhythmia[J].1999,97(2).
[7]Balser JR,Viswanathan PC,Benson DW.A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation.[J].2003,111(3).
[8]Schott JJ,Hulsbeek M,Probst V,etc.Cardiac conduction defects associate with mutations in SCN5A.[J].1999,23(1).
[9]Carmen R. Valdivia,Jonathan C. Makielski,Bin Ye,etc.A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation[J].2003,12(0).
[10]Duangrurdee Wattanasirichaigoon,Mark R. Vesely,Priya Duggal,etc.Sodium channel abnormalities are infrequent in patients with long QT Syndrome: Identification of two novel <em>SCN5A</em> mutations[J].1999,86(5).