Chen Junhua, Sun Fuqiang, Fu Jia, Zhang Hongyan
Department of Pediatrics, Second Hospital of Tianjin Medical University, 23 Pingjiang Street, Hexi District, Tianjin, 300211, China.
Pediatr Cardiol. 2015 Apr;36(4):737-42. doi: 10.1007/s00246-014-1073-5. Epub 2014 Dec 9.
As a transcription factor mainly expressed in cardiovascular system, T-box 20 (TBX20) plays an important role in embryonic cardiovascular system development and adult heart function. Previous studies have identified associations of two SNPs in the T-box DNA-binding domain of TBX20 with congenital heart disease (CHD) in two Caucasian families, but the associations of TBX20 mutations underlying the more common populations with CHD remain to be uncovered. In this study, 25 unrelated Chinese Han neonates with CHD and 25 healthy children as controls were investigated for TBX20 mutations. SNP genotyping was performed by PCR-DNA sequencing. The selected SNPs were well genotyped and SNP rs3999941 was found to be strongly associated with CHD (p = 0.007). The minor allele of rs3999941 showed a high-risk factor for CHD (OR 4.24; 95 % CI 1.41-12.71). Besides, we found a new SNP site located at the 657th nucleotide of the exon 5 of TBX20 gene which may also be associated with CHD, c.657A>C. The frequency was significantly different between two groups (p = 0.011), the minor allele of SNP c.657A>C also showed a risk factor for CHD (OR 2.56; 95 % CI 1.02-6.46). These findings suggested that the TC genotype of SNP rs3999941 and AC genotype of the new SNP c.657A>C in the TBX20 gene may be risk factors for CHD and thus screening of these SNPs may have some implications in the prevention and treatment of CHD in Han Chinese children.
作为一种主要在心血管系统中表达的转录因子，T盒20（TBX20）在胚胎心血管系统发育和成年心脏功能中发挥着重要作用。先前的研究已经在两个白种人家庭中确定了TBX20的T盒DNA结合域中的两个单核苷酸多态性（SNP）与先天性心脏病（CHD）的关联，但在更常见人群中TBX20突变与CHD的关联仍有待发现。在本研究中，对25名患有CHD的非相关中国汉族新生儿和25名健康儿童作为对照进行了TBX20突变研究。通过聚合酶链反应- DNA测序进行SNP基因分型。所选的SNP进行了良好的基因分型，并且发现SNP rs3999941与CHD密切相关（p = 0.007）。rs3999941的次要等位基因显示为CHD的高危因素（比值比4.24；95%可信区间1.41 - 12.71）。此外，我们发现一个位于TBX20基因外显子5第657个核苷酸处的新SNP位点，其也可能与CHD相关，即c.657A>C。两组之间该位点频率有显著差异（p = 0.011），SNP c.657A>C的次要等位基因也显示为CHD的危险因素（比值比2.56；95%可信区间1.02 - 6.46）。这些发现表明，TBX20基因中SNP rs3999941的TC基因型和新SNP c.657A>C的AC基因型可能是CHD的危险因素，因此对这些SNP的筛查可能对中国汉族儿童CHD的防治具有一定意义。
