Association of TBX5 gene polymorphism with ventricular septal defect in the Chinese Han population
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 1
- DOI:
- 10.3760/cma.j.issn.0366-6999.2009.01.006
- Key Word:
- ventricular septal defect;congenital heart disease;TBX5;single nucleotide polymorphism;haplotype
Abstract： Background Congenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population. Methods One hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to 15erform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method. Results The TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P=0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P=0.05, multiple loci regression analyses based on reconstructed haplotype blocks). Conclusions TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Hart Chinese. This finding has set a direction for further genetic and functional studies.
- [1]宫立国,邱广蓉,邱广斌,等.人类单纯性先天性心脏病中TBX5基因的突变及表达研究[J].2003,(5).
- [2]Plageman TF Jr,Yutzey KE.Differential expression and function of Tbx5 and Tbx20 in cardiac development.[J].2004,279(18).
- [3]B G, Bruneau,G, Nemer,J P, Schmitt,etc.A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease.[J].2001,106(6).
- [4]Q Y, Li,R A, Newbury-Ecob,J A, Terrett,etc.Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family.[J].1997,15.
- [5]Stennard FA,Harvey RP.T-box transcription factors and their roles in regulatory hierarchies in the developing heart.[J].2005,132(22).
- [6]Nemer M.Genetic insights into normal and abnormal heart development.[J].2008,17(1).
- [7]K M, Law,K T, Tse.Prenatal sonographic diagnosis of familial Holt-Oram syndrome associated with type B interrupted aortic arch.[J].2008,14(4).
- [8]Price BM,Brown DD,Goetz SC,etc.Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis.[J].2005,132(3).
- [9]Altshuler D,de Bakker PI,Daly MJ,etc.Efficiency and power in genetic association studies.[J].2005,37(11).
- [10]C T, Basson,D R, Bachinsky,R C, Lin,etc.Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome.[J].1997,15.
- [11]Mori AD,Bruneau BG.TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed.[J].2004,19(3).
- [12]Lerone M,Romeo G,Quadrelli R,etc.Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations.[J].1999,96(6).
- [13]Ransom J,Srivastava D.The genetics of cardiac birth defects[J].2007,18(1).
- [14]Shen A,Zhang W,Li X.GATA4 mutations in 486 Chinese patients with congenital heart disease.[J].2008,51(6).
- [15]Simon HG,Dettman RW,Bimber B.Differential regulation of Tbx5 protein expression and sub-cellular localization during heart development.[J].2007,302(1).
- [16]S, Pabst,B, Wollnik,E, Rohmann,etc.A novel stop mutation truncating critical regions of the cardiac transcription factor NKX2-5 in a large family with autosomal-dominant inherited congenital heart disease.[J].2008,97(1).
- [17]Srivastava D,Obler D,Shen J,etc.Spectrum of heart disease associated with murine and human GATA4 mutation.[J].2007,43(6).
- [18]Plageman TF Jr,Yutzey KE.Microarray analysis of Tbx5-induced genes expressed in the developing heart.[J].2006,235(10).
- [19]Smith ML,Ritchie ME,Tavare S,etc.beadarray: R classes and methods for Illumina bead-based data[J].2007,23(16).
- [20]Tomita-Mitchell A,Morris CD,Goldmuntz E,etc.GATA4 sequence variants in patients with congenital heart disease.[J].2007,44(12).
- [21]Sebastio G,Superti Furga A,Melis D,etc.Holt-Oram syndrome associated with anomalies of the feet.[J].2008,146A(9).
- [22]Nowotschin S,Liao J,Aggarwal VS.Identification of downstream genetic pathways of Tbx1 in the second heart field.[J].2008,316(2).