新疆维吾尔族人群SCN5A基因在单纯性先天性心脏病中的相关性分析

Association between SCN5A gene polymorphism and simple congenital heart disease in Xinjiang Uyghur populations

背景:SCN5A是目前报道最多的编码心肌钠离子通道的基因,SCN5A基因编码人心脏电压门控钠通道的α亚基,在人心肌细胞中高度表达,其主要负责动作电位的产生和兴奋细胞的扩展,对控制心肌细胞的兴奋传导起着关健作用。目的:研究SCN5A基因H588R,C5457T,R1193Q位点多态性与新疆地区维吾尔族单纯性先天性心脏病的相关性。方法:选取150例新疆维吾尔族单纯性先天性心脏病患者作为病例组,150例新疆维吾尔族健康人群作为对照组。采用聚合酶链式反应-限制性片段长度多态性分析技术和直接测序法对SCN5A基因H588R,C5457T,R1193Q位点进行多态性检测,分析不同基因型频率和等位基因频率在病例组和对照组中的分布。结果与结论:两组比较多态位点C5457T,R1193Q的基因型频率和等位基因频率差异均有显著性意义(P<0.05);多态位点H588R的基因型频率差异有显著性意义(P<0.05),而等位基因频率差异无显著性意义(P﹥0.05)。与对照组比较,C5457T位点在房间隔缺损和动脉导管未闭患者中等位基因频率分布差异有显著性意义(P<0.05),等位基因T分布增加房间隔缺损、动脉导管未闭的发病风险,OR值分别为3.636和3.467。R1193Q位点在房间隔缺损、法洛氏四联症和卵圆孔未闭患者中等位基因频率分布差异有显著性意义(P<0.05),等位基因A分布增加房间隔缺损、法洛氏四联症和卵圆孔未闭的发病风险,OR值分别为3.413,3.839和4.059。结果证实,SCN5A基因多态位点C5457T,R1193Q可能是新疆维吾尔族单纯性先天性心脏病的易感因子;未发现多态位点H558R与新疆维吾尔族单纯性先天性心脏病直接相关。

BACKGROUND：SCN5A is the gene encoding the largest reported cardiac sodium channel, andαsubunit of SCN5A gene encoding human cardiac voltage-gated sodium channels is highly expressed in human myocardial cel s, which is mainly responsible for generation of action potentials and expansion of excitable cel s, and plays an important role in control ing excitability conduction of myocardial cel s. OBJECTIVE：To explore the correlation between the polymorphism loci of H588R, C5457T, R1193Q of the SCN5A gene and simple congenital heart disease in Xinjiang Uyghur populations. METHODS：150 patients with simple congenital heart disease in Xinjiang Uygur served as case group, and another 150 Xinjiang Uygur healthy people as control group. Polymerase chain reaction-restriction fragment length polymorphism analysis and direct sequencing method were chosen to detect the H588R, C5457T, R1193Q polymorphism loci of SCN5A gene, and to analyze the distribution of different genotypes and al ele frequencies in the case group and the control group. RESULTS AND CONCLUSION：The genotype and al ele frequencies at polymorphic loci of C5457T and R1193Q were significant different between the case and control groups （P〈0.05）. Genotype frequencies of polymorphic locus of H588R were significantly different between the two groups （P〈0.05）. Compared with the control group, the polymorphic locus of C5457T in patients with atrial septal defect and patent ductus arteriosus showed significant difference in the al ele frequency （P〈0.05）, and al ele T increased the onset risks for atrial septal defect and patent ductus arteriosus （odd ratio=3.636, 3.467）. There were significant differences in al ele frequency at the polymorphic loci of R1193Q among patients with atrial septal defect, tetralogy of Fal ot and patent foramen ovale （P〈0.05）, and al ele A increased the onset risks for atrial septal defect, tetralogy of Fal ot and patent foramen ovale （odd ratio=3.413, 3.839, 4.059）. The polymorphism loci of C5457T, R1193Q of SCN5A gene may be the susceptibility factors for simple congenital heart disease in Xinjiang Uygur populations. The polymorphic locus of H558R is not directly related to simple congenital heart disease in Xinjiang Uygur populations.