TBX1启动子区核苷酸变异与心脏圆锥动脉干畸形相关性研究

摘要

Objective To explore the correlation between mutations in the promoter region of TBX1 gene and conotruncal heart defects. Methods A total of 621 children with conotruncal heart defects were recruited. Multiplex ligation-dependent probe ampliifcation (MLPA) was used to detect the copy numbers of chromosomal region 22 q 11 . 2 . Children with 22 q 11 . 2 deletion were excluded. Polymerase chain reaction ampliifcation (PCR) and gene sequencing were applied to analyze promoter region of TBX 1 (-2000 ..+1 ) in 605 children with conotruncal heart defects without 22 q 11 . 2 deletion and 588 healthy children. Bioinformatics software was used to predict and analyze the function of the variable loci. Results There were mutations in the promoter region of TBX 1 gene in children with conotruncal heart defects, including 3 single nucleotide polymorphisms (SNP) sites and 7 rare loci. The incidence of mutation was 1 . 7%. The analysis of 7 rare loci by AliBaba 2 . 1 to showed that 3 of them may inlfuence the combination of trans-acting factors and cis-acting elements of the promoter of TBX 1 gene. Conclusion The mutation in the TBX 1 promoter region may be related to the occurrence of conotruncal heart defects.%目的：验证TBX 1启动子区核苷酸变异与心脏圆锥动脉干畸形的相关性。方法招募621例心脏圆锥动脉干畸形患儿，采用MLPA方法检测患儿22 q 11.2区基因组DNA的拷贝数，排除22 q 11.2微缺失患儿。对605例无22 q 11.2微缺失的心脏圆锥动脉干畸形患儿和588例正常对照儿童，采用PCR扩增和基因测序方法，进行TBX 1启动子区序列分析（-2000..+1），并应用生物信息学软件对变异位点进行功能预测分析。结果心脏圆锥动脉干畸形患儿中发现存在TBX 1基因启动子区位点变异，其中包括3个已报道的单核苷酸多态性（SNP）和7个罕见变异位点，突变的发生率约为1.7%。应用AliBaba 2.1对7个罕见变异位点进行分析，显示其中3个位点可能影响相关反式作用因子与TBX 1启动子区顺式作用元件的结合。结论 TBX 1启动子区核苷酸变异可能与心脏圆锥动脉干畸形发生相关。