RESUMO
Ventricular septal defect (VSD) is the most common form of cardiac malformations accounting approximately 20% of all congenital heart defects. SMAD7 is an inhibitory protein that antagonizes the signalling of TGF-ß family member and has been found in the development and function of mouse heart models. This study aims to screen and identify the polymorphisms of SMAD7 exonic regions in Malay population with VSD. Peripheral blood samples were collected and extracted from 30 clinically diagnosed VSD patients. PCR amplification was performed using 12 sets of designed primers encompassing seven exons of SMAD7. Re-sequencing was conducted to characterize the polymorphisms of SMAD7. Observed polymorphisms were then genotyped in 30 healthy individuals using both re-sequencing and allele-specific PCR techniques. A total of 10 variants were identified in the patient population located in the upstream (rs7236774), exonic (rs368427729, rs145686330, rs3764482, rs3809922, rs780863704 and rs3809923), intronic (rs3736242) and 3'UTR regions (rs375444823 and rs16950113). No significant difference of genotype and allele frequency was observed among these SNPs. Two synonymous variants (rs3809922 and rs3809923) were found in complete linkage disequilibrium (r2=1.0) with each other indicate a strong correlation of these SNPs. The identification of these SNPs provides a new perspective of the VSD causation.