中国汉族人群心脏钠离子通道基因SCN5A多态性及其与特发性室性心律失常关系的研究

A study on the relationship between genetic polymorphisms of the human cardiac sodium channelαsubunit SCN5A gene and idiopathic ventricular arrhythmia in a Chinese Han population

目的：研究中国汉族人群心脏钠离子通道α亚单位(voltage-gated sodium channel type V,SCN5A)基因的遗传多态性及其与特发性室性心律失常(idiopathic ventricular arrhythmia,IVA)的关系。方法：应用PCR直接测序技术测定21例IVA患者和103名中国汉族健康对照人群SCN5A基因编码区外显子、外显子-内含子交界区以及3′侧翼区序列,确定并比较其单核苷酸多态性(single nucleotide polymorphisms,SNPs)、基因型和等位基因频率分布。结果：在中同汉族健康人群及IVA患者中共检测到10个遗传变异,5个为新发现的遗传变异,分别为c．1676C＞T(p．Thr559Ile)、c．6210C＞T、c．6804C＞T、c．7013T＞A和c．7014C＞T,其中前2个变异在2个不同的健康个体中发现,其等位基因频率仅0．005。两组中各SNP等位基因在人群中的分布均符合Hardy-Weinberg平衡。其中c．87G＞A(p．Ala29Ala)和c．1673A＞G(p．His558Arg)2个SNPs等位基因频率在健康对照组男女之间存在差异(P=-0．023,P=0．027)；另外,女性IVA患者87A等位基因频率明显高于健康女性(0．500：0．198,P=0．005)。男性IVA患者1673G等位基因频率(0/20)明显低于健康男性(0．175)(P=0．043)。结论：本研究发现c．87G＞A和c．1673A＞G等位基因在中国汉族健康人群不同性别中的分布不同：提示等位基因87A可能是女性IVA患者的一个遗传易感因素,等位基因1673G在男性中可能具有预防室性心律失常作用。

Objective To investigate the relationship between the genetic polymorphisms of the human cardiac sodium channel α subunit gene （voltage-gated sodium channel type V, SCN5A） and the occurrence of idiopathic ventricular arrhythmia （IVA）. Methods Genotyping for polymorphic variance of SCN5A gene was detected by polymerase chain reaction （PCR） and automated Genescan sequencing analysis in 21 unrelated Chinese IVA patients and 103 healthy controls. Results Ten genetic variations were found, and 8 of them manifested single nucleotide polymorphisms （SNPs）. Among the polymorphic variations observed in this study, 5 polymorphisms were reported for the first time, which were c. 1676C〉T （p.Thr559Ile）, c.6210C〉T, c.6804C〉T, c.7013T〉A and c.7014C〉T respectively. The detected SNPs allele frequencies in the both groups markedly accorded with Hardy-Weinberg equilibrium. Two novel variations, c.1676C〉 T （p. Thr559Ile） and c.6210C〉T, were heterozygous in two different healthy controls, revealing a frequency of 0.005, but not in IVA patients. The allele frequenees of two SNPs, c.87G〉A （p.Ala29Ala） and c.1673A〉G （p.His558Arg）, were significantly higher in the male controls than those in the female controls （P=0.023, P=0.027）. In addition, significant difference was noted in the allele frequency of c.87G〉A between the female IVA patients （0.500） and the female controls （0.198） （P= 0.005）. The allele frequency of c. 1673A〉G was significantly lower in the male IVA patients （0/20） than that in the male controls （0.175） （P=0.043）. Conclusions Significant difference exists in the distribution of two SNPs c.87G〉A and c.1673A〉G between the males and the females in a Chinese Han population. The 87A allele might be associated with an increased risk of IVA in the female patients, and the 1673G allele may be protective against ventricular arrhythmia in the males.Further studies are needed to prove our findings.