中国南方汉族人群SCN5A基因H558R、R1193Q、C5457T及3666+69G＞C多态性与青壮年猝死综合征的相关性研究

Research on the relationship between SUNDS and single nucleotide polymorphisms of SCN5A gene in South Chinese Han population

目的研究中国南方汉族人群心脏钠离子通道α亚单位(SCN5A)基因的H558R、R1193Q、C5457T及3666+69G>C单核苷酸多态性(SNPs)与青壮年猝死综合征(SUNDS)的关系。方法应用多聚酶链反应(PCR)直接测序技术,检测SUNDS猝死者(SUNDS组)及中国南方汉族健康男性(健康对照组)SCN5A基因Exon12、Exon14、Exon18、Exon20、Exon26和Exon28的一部分,采用病例对照分析H558R、R1193Q、C5457T、3666+69G>C与SUNDS的相关性,比较H558R基因型、少见等位基因频率分布在不同性别是否存在差异。结果SUNDS组和健康对照组共检测到13个多态位点,3666+69G>C、4437+361T>C为本研究新发现的多态位点,其中SUNDS组和健康对照组D1819D、3666+69G>C差异具有统计学意义(P均<0.01)。不同性别组中,H558R少见等位基因频率分布差异没有统计学意义。结论SCN5A基因多态位点D1819D、3666+69G>C可能是男性人群罹患SUNDS的易感因子,未发现多态位点H558R、R1193Q与SUNDS直接相关。

Objective To investigate single nucleotide polymorphisms of the human cardiac sodium channel α- subunit gene（ Voltage-gated sodium channel type V, SCN5A） and the relationship with sudden unexplained nocturnal death syndrome（SUNDS） in South Chinese Han population. Methods A case-control design was applied in this research. Genotyping polymorphisms of SCN5A gene was detected by polymerase chain reaction （PCR） and direct sequencing analysis in sporadic SUNDS cases, healthy male controls which were recruited from Guangdong province. Results Thirteen polymorphisms of SCN5A gene were found, among which, 2 pol- ymorphisms of 3666 ＋69G 〉 C, 4437 ＋361T 〉 C were reported for the first time. The allele frequencies of two SNPs： D1819D, 3666 ＋69G 〉 C were significantly higher in SUNDS cases than those in the male controls （P=0.0015, P=0.0011）. Conclusions Thepolymorphisms of D1819D, 3666＋69G 〉 CofSCN5Agene may be the risk factors of the occurrence of Chinese SUNDS.