我国成年人HERG基因EXON7-1692位点基因多态性与QT间期关系研究

Study on the relationship between polymorphism of HERG gene EXON7-1692 and QT interval in adult Chinese population

目的在一特定中国人群中,探讨心肌钾通道基因HERG基因EXON7-1692位点多态性与成年期QT间期的关系。方法对该人群344人进行临床检测,记录标准12导联心电图,计算校正的QT间期(QTc);用聚合酶链反应(PCR)扩增QT间期相关基因HERG第七外显子(EXON7),其扩增产物直接进行单核苷酸序列分析。结果QTc≤0.41s者(健康对照组)为267人,占调查人群的77.6%;QTc>0.41s者(QT间期延长组)为77人,占调查人群的22.4%。在EXON7-1692位点测得单核苷酸多态性,其中,纯合GG基因型241人,占70.1%,基因频率为0.839;纯合AA基因型8人,占2.3%,基因频率为0.161;杂合GA基因型95人,占27.6%,符合Hardy-Weinburg平衡(χ=0.158,2ν=3-2=1,0.5<P<0.75)。三种基因型在健康对照组和QT间期延长组的分布频率差异没有统计学意义(χ=0.9,P=20.6)。结论该人群HERG基因EXON7-1692位点的多态性与临床QT间期无明显直接相关。

Objective To understand the relationship between the QT in terval and the polymorphism of myocardial potassium channel HERG gene on an population-based study in middle-aged Chinese population. Methods A standard 12-lead ECG was recorded and the corrected QT (QTc) was calculated accordingly by BAZETT formula.Polymerase chain reaction(PCR) was used to amplify the exon7 of the HERG gene related to QT interval,and all amplified products were analyzed by direct sequencing. Results QTc values of≤0.41 s defined as control group were found in 267 of the 344 cases(77.6%),and those of >0.41 s defined as the group of prolonged QT interval were found in the remainder (22.4%).There were three genotypes of single nucleotide at the site of 1692 in EXON 7 of HERG gene.In 241 of the 344 cases(70.1%),homozygote genotype of GG phenotype was found with a gene frequency of 0.839,8 cases(2.3%) showed homozygote genotype of AA phenotype with a gene frequency of 0.161,and the other 95 cases(27.6%) showed heterozygote genotype of GA phenotype.The data were in agreement with the test of Hardy-Weinburg balance (χ2=0.158,ν=3-2=1,0.5<P<0.75).The genotype frequency of AA,GG and GA found in the prolonged QT interval group was 2.6%,74.0% and 23.4%,respectively;for the control group the frequency was 2.3%,68.9% and 28.8%,respectively.The frequency of three genotypes was found of no difference in two groups(χ2=0.9,P=0.6). Conclusion No direct relationship was found bewteen the single nucleotide polymorphism(SNP) at the site of 1692 in EXON 7 of HERG gene and the clinical QT intervals in this middle-aged Chinese population.