节点/TGF-Lefty信号通路基因变异在先天性心脏病中可能作用的特征分析。
Characterization of nodal/TGF-lefty signaling pathway gene variants for possible roles in congenital heart diseases.
作者信息
Deng Xia, Zhou Jing, Li Fei-Feng, Yan Peng, Zhao Er-Ying, Hao Ling, Yu Kai-Jiang, Liu Shu-Lin
机构信息
Genomics Research Center (one of the State-Province Key Laboratory of Biopharmaceutical Engineering, China), Harbin Medical University, Harbin, China.
Intensive Care Unit, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
出版信息
PLoS One. 2014 Aug 11;9(8):e104535. doi: 10.1371/journal.pone.0104535. eCollection 2014.
BACKGROUND
Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD).
METHODS
We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software.
RESULTS
Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
CONCLUSIONS
The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.
背景
Nodal/TGF-Lefty信号通路在人类胚胎干细胞分化的早期阶段对引导其分化为不同的胚胎谱系具有重要作用。LEFTY是Nodal/TGF-Lefty信号通路中的转化生长因子之一，在心脏发育中起重要作用。本研究的目的是寻找Lefty基因变异是否与先天性心脏病（CHD）相关的证据。
方法
我们对230名中国汉族CHD患者的Lefty基因进行了测序，并评估了位于基因翻译区域内的单核苷酸多态性（SNP）rs2295418、rs360057和g.G169A。使用SPSS（版本13.0）中的卡方检验进行统计分析。使用在线软件OEGE对人群进行哈迪-温伯格平衡检验，并使用Vector NTI软件对LEFTY蛋白进行多序列比对。
结果
在Lefty1基因中鉴定出两个杂合变异，g.G169A和g.A1035C，在Lefty2基因中鉴定出一个杂合变异，g.C925A。统计分析表明，Lefty2基因中的rs2295418（g.C925A）变异与CHD风险显著相关（P值 = 0.016<0.05）。Lefty1基因中rs360057（g.A1035C）变异的基因型频率与CHD风险相关（P值 = 0.007<0.05），但等位基因频率不相关（P值 = 0.317>0.05）。
结论
Lefty2基因中的SNP rs2295418与中国汉族人群的CHD相关。
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