DNA sequencing of TGFβ2 in sporadic patients with tetralogy of Fallot

Transforming growth factor β2 (TGFβ2) plays an essential role in cardiac morphogenesis. However, the prevalence of TGFβ2 mutations in congenital heart disease (CHAD) and the correlation between the TGFβ2 genotype and the CHAD phenotype have not been studied extensively. The aim of this study was to examine DNA sequence changes in the TGFβ2 gene in sporadic patients with tetralogy of Fallot (TOF), and to observe whether TGFβ2 is the susceptibility gene for TOF. A cohort of 100 pediatric patients with TOF was recruited to the study; 200 healthy children were used as controls. PCR and genotyping were conducted for the detection of DNA changes in TGFβ2. The exons and the 5′ untranslated region (5′UTR) sequences of the TGFβ2 gene were amplified. No mutations were identified in the coding region in any of the TOF patients. However, three single nucleotide changes, including 9126 A>AC, 9353 A>AG and 9040_9043 del CTTC, in the 5′UTR were found. There were no significant differences in allelic frequencies and genotype frequencies of position 9126 and 9353 between the TOF group and the control group. On the contrary, a significant difference was identified in the allelic frequencies (χ2=17.469, P<0.001) of position 9040_9043 in the 5′UTR between the TOF group and the control group. Our results suggest that TGFβ2 may be a potential candidate gene of TOF. SNPs at position 9040_9043 del CTTC in the 5′UTR of TGFβ2 may be associated with susceptibility to TOF. The CTTC allele may be the susceptibility allele for TOF. However, the exact effect of these sequence changes requires further study using functional experiments.