SCN5A基因单核苷酸多态性与壮族原发性癫痫易感性的相关分析
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摘要
目的探究SCN5A基因单核苷酸多态性(SNP)与壮族原发性癫痫易感性的相关性。方法应用病例对照研究,收集广西百色地区确诊的原发性癫痫患者155例作为研究对象,同期健康体检者200例作为对照组,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术和直接测序法对患者外周血SCN5A基因中rs6599230和rs1805126位点基因多态性检测,评估两组患者不同基因型和等位基因的分布频率与癫痫易感性的关联性。结果 rs6599230和rs1805126位点均检测到CT、TT和CC 3种基因型。癫痫组与对照组相比,rs6599230等位基因分布(χ~2=11.030,P=0.001)和基因型分布(χ~2=11.147,P=0.004)的差异均具有统计学意义;rs1805126等位基因分布(χ~2=0.080,P=0.928)和基因型分布(χ~2=0.786,P=0.675)的差异均无统计学意义。与CC+CT基因型相比,rs6599230位点的TT基因型显著增加了癫痫发病的危险性(OR=1.921,95%CI:1.230～2.998)。结论 SCN5A基因rs6599230位点SNP可能与壮族原发性癫痫易感性有关。
Objective To investigate theassociation between the single nucleotide polymorphisms of SCN5 A genes and the susceptibility in Zhuangzu idiopathic epilepsies. Methods A case-control study was performed. One hundred and fifty-five Zhuangzu idiopathic epilepsies patients diagnosed in Baise,Guangxi,and two hundred healthy subjects were recruited. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique and the way of direct sequencing were used to determine the genotypes of the rs6599230 and rs1805126 locus of SCN5 A gene. The correlation between the genotype and alleles of the two groups and the susceptibility of epilepsies were evaluated. Results 3 genotypes of CT,TT and CC were respectively detected in rs6599230 and rs1805126 locus. Compared with the control group,the differences in the allele distribution(χ~2=11.030,P = 0.001)and genotype distribution(χ~2= 11.147,P = 0.004)of the rs6599230 locus in the epilepsies group were statistically significant. There was no significant difference in allele distribution(χ~2= 0.080,P = 0.928)and genotype(χ~2= 0.786,P = 0.675)in rs1805126 locus. Compared with the CC+CT genotype,the TT genotype at rs6599230 locus significantly increased the susceptibility of epilepsies(OR = 1.921,95%CI 1.230 ～ 2.998).Conclusion These results suggest that the single nucleotide polymorphisms of rs6599230 in SCN5 A genes may be associated with the susceptibility in Zhuangzu idiopathic epilepsies.
Objective To investigate theassociation between the single nucleotide polymorphisms of SCN5 A genes and the susceptibility in Zhuangzu idiopathic epilepsies. Methods A case-control study was performed. One hundred and fifty-five Zhuangzu idiopathic epilepsies patients diagnosed in Baise,Guangxi,and two hundred healthy subjects were recruited. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique and the way of direct sequencing were used to determine the genotypes of the rs6599230 and rs1805126 locus of SCN5 A gene. The correlation between the genotype and alleles of the two groups and the susceptibility of epilepsies were evaluated. Results 3 genotypes of CT,TT and CC were respectively detected in rs6599230 and rs1805126 locus. Compared with the control group,the differences in the allele distribution(χ~2=11.030,P = 0.001)and genotype distribution(χ~2= 11.147,P = 0.004)of the rs6599230 locus in the epilepsies group were statistically significant. There was no significant difference in allele distribution(χ~2= 0.080,P = 0.928)and genotype(χ~2= 0.786,P = 0.675)in rs1805126 locus. Compared with the CC+CT genotype,the TT genotype at rs6599230 locus significantly increased the susceptibility of epilepsies(OR = 1.921,95%CI 1.230 ～ 2.998).Conclusion These results suggest that the single nucleotide polymorphisms of rs6599230 in SCN5 A genes may be associated with the susceptibility in Zhuangzu idiopathic epilepsies.
引文
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[2]TSUKAKOSHI T,LIN L,MURAKAMI T,et al.Persistent QTprolongation in a child with gitelman syndrome and SCN5AH558R polymorphism[J].Int Heart J,2018,59(6):1466-1468.
[3]OU SW,KAMEYAMA A,HAO LY,et al.Tetrodotoxin-resistant Na+channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCNA5[J].Eur J Neurosci,2005,22(4):793-801.
[4]QURESHI S F,ALI A,JOHN P,et al.Mutational analysis of SCN5A gene in long QT syndrome[J].Meta Gene,2015,2(6):26-35.
[5]SHAN L,MAKITA N,XING Y,et al.SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia[J].Mol Genet Metab,2008,93(4):468-474.
[6]常琳.中国癫痫流行病学调查研究进展[J].国际神经病学神经外科学杂志,2012,39(2):161-164.
[7]DO T T,VU D M,HUYNH T T,et al.SCN1A gene mutation and adaptive functioning in 18 vietnamese children with dravet syndrome[J].J Clin Neurol,2017,13(1):62-70.
[8]O′BRIEN J E,MEISLER M H.Sodium channel SCN8A(Nav1.6):properties and de novo mutations in epileptic encephalopathy and intellectual disability[J].Front Genet,2013,4(1):213.
[9]DENHAM N C,PEARMAN C M,DING W Y,et al.Systematic re-evaluation of SCN5A variants associated with Brugada syndrome[J].Int J Cardiol,2018,15(3):271-278.
[10]叶尔肯别克·沙德克,木胡牙提·乌拉斯汗,刘志强,等.SCN5A基因H558R位点多态性与新疆地区维吾尔族心房颤动的相关性研究[J].临床心血管病杂志,2016,32(11):1102-1106.
[11]王军,宗志红,欧绍武,等.编码脑组织Nav1.5钠通道新外显子的克隆、鉴定和分布[J].生物化学与生物物理进展,2007,34(3):255-259.
[12]REN C T,LI D M,OU S W,et al.Cloning and expression of the two new variants of Nav1.5/SCN5A in rat brain[J].Mol Cell Biochem,2012,365(1-2):139-148.