1f68e7de-096b-4068-b87a-df10c157d752
title
Single nucleotide polymorphisms of the  SCN5A  gene in Han Chinese and their relation with Brugada syndrome.
68872a56-83a9-4162-be79-dc0b42e466c7
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.