In this work, we found that the variant rs2289263 before the 5’UTR of SMAD3 gene was associated with increased risk of VSD in the Chinese Han population, while in a previous study, we demonstrated that rs2295418 (g.C925A) in Lefty2 gene is associated with the risk of CHD [1]. This evidence concerns the gene SMAD3 and ventricular septal defect.