先天性心脏病与同源蛋白NKX2．5基因突变的关系

Association of NKX2. 5 gene with congenital heart disease in Guangxi Zhuang population

目的探讨同源蛋白NKX2.5（NKX2.5）基因突变和广西壮族人群先天性心脏病（CHD）的关系。方法应用聚合酶链反应以及DNA测序技术，对30例广西壮族CHD患者（包括房间隔缺损组8例，室间隔缺损组10例，法洛四联征5例，右室双出口2例，大动脉转位1例，肺动脉狭窄1例）以及30正常非CHD对照者（正常对照组）的NKX2.5基因的全部外显子和侧翼序列进行突变检测，并对单核苷酸多态性（SNP）位点进行基因分型，分析单个位点的基因性和等位基因频率与CHD是否有关。结果所有CHD患者基因编码均未发现突变，而在NKX2.5基因外显子1区域发现1个SNP位点，这个位点位于上游63位碱基63A〉G，导致第21位密码子由GAA转变成GAG，碱基替换后仍然编码谷氨酸（Glu），属于同义突变。基因型频率和等位基因频率的分布，在CHD组和正常对照组之间差异无统计学意义（两组基因型频率比较，χ2＝1.725，P＝0.422；等位基因频率比较，χ2＝1.714，P＝0.190）。结论NKX2.5基因突变与我国广西地区壮族CHD之间无明显相关，该基因上的63A〉G的SNP与先天性心脏病之间无明显相关。

Objective To investigate the relationship between NKX2.5 gene mutation and congenital heart diseases （CHD） in Guangxi Zhuang population.MethodsA cohort of 30 cases of CHD in Guangxi Zhuang Autonomous Region （including 8 cases of atrial septal defect, 10 cases of ventricular septal defect, 5 cases of tetralogy of Fallot, 2 cases of double outlet right ventricle, 1 case of transposition of the great arteries, and 1 case of pulmonary artery） and 30 cases of normal non-CHD as controls （normal control group） werer egistered. The complete exons and flanking partial introns of the candidate gene NKX2-5 were amplified by polymerase chain reaction and the amplicons were sequenced using the di-deoxynucleotide chain termination procedure. We also analyzed 30 non-CHD subjects as normal controls to compare whether Nkx2.5 gene or single nucleotide polymorphism （SNP） raleted to simple CHD.ResultsDirect sequencing of Nkx 2.5 gene code from all samples showed no mutations. While we found an A-to-G transition at nucleotide 63 in exon 1 of Nkx2.5 gene, indicating a synonymous mutations at codon 21 （Glu21Glu）. Further study presented that there were no statistically significant differences in Nkx2.5 genotype frequency and allele frequency between CHD and normal controls, respectively （Comparison of genotype frequency in the two groups, χ2=1.725, P=0.422; Comparison of allele frequency, χ2=1.714, P=0.190）.ConclusionOur study indicates that Nkx2.5 gene mutations may not be related to simple CHD, while its genotype allele distribution may not be related to CHD, too.