A regulatory variant in TBX2 promoter is related to the decreased susceptibility of congenital heart disease in the Han Chinese population.

Background Tbx2 plays a vital role in the cardiac cushion development. In this study, we aimed to determine the relationship between common genetic variants in the promoter region of TBX2 gene and the risk of congenital heart disease (CHD). Methods Blood samples of 516 CHD patients and 587 control subjects were enrolled. Sanger sequencing and SNaPshot analysis were performed for genotyping in our case-control cohort. Luciferase and electrophoretic mobility shift assay (EMSA) were conducted to uncover the potential modulatory mechanism of the related variants. Results Variant rs4455026(c.-1028G>C) in TBX2 promoter region was found to be associated with significantly lower CHD susceptibility. The risk of CHD in C allele carriers (GC and CC genotypes) decreased by 30% compared to the wild-type GG genotype subjects (OR = 0.70, 95% CI = 0.55-0.89, p = 0.0038). It was revealed that G to C variation resulted in a decrease in the transcriptional activity of luciferase gene, and a potential change in binding affinity with certain nucleoproteins in EMSA data. Conclusion The minor C allele of rs4455026 in TBX2 promoter region was related with lower CHD susceptibility in the Han Chinese population via repressing its transcriptional activity.