BACKGROUNDCongenital 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.

METHODSOne 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 perform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method.

RESULTSThe 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).

CONCLUSIONSTBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese. This finding has set a direction for further genetic and functional studies.