Objectives: To investigate the association between promoter methylation of the TBX20 gene and tetralogy of Fallot (TOF)． Methods. The methylation level of TBX20 promoter regions in 23 patients with TOF and five controls were analyzed through bisulfite sequencing polymerase chain reaction. Meanwhile, the expression of TBX20 mRNA was measured using real time fluorescence quantitative polymerase chain reaction.
Results: The region -400 to -48 in the TBX20 promoter consisting of 42 CpG sites was predicted to contain multiple transcription factor binding sites. In this study, the overall methylation level in this region was lower in patients with TOF than in the controls (P = .035). Among the 42 CpG sites, the methylation percentages of the CpG 26 site in the TOF cases were lower than those in the controls (P = .016). The mRNA expression of TBX20 in the right ventricular outflow tract myocardium was increased in TOF cases in contrast to those in the controls (P < .001). The methylation levels in TOF cases were correlated with mRNA expression values (r = -0.81, P < .001).
Conclusion: The downregulated methylation level at TBX20 promoter may be responsible for the elevated mRNA expression levels in patients with TOF. The abnormal methylation status of the TBX20 promoter may contribute to the pathogenesis of TOF.
Keywords: TBX20; gene; methylation; promoter; tetralogy of Fallot.