Objective:To investigate the association and potential mechanism between single nucleotide polymorphism (SNP)in 3′untranslated region(3′-UTR) of COL6A2 and the risk of congenital atrial septal defect(ASD). Methods:SNPs in 3′-UTR of COL6A2 were searched in PubMed and Hapmap database for minimum allele frequency (MAF)>0.05 in Han Chinese population. Then the potential functional SNPs were predicted in website of miRNA-SNP. Meanwhile,the association between SNPs and the risk of ASD was checked in our previous Genome-wide association study (GWAS) database of congenital septation defects. Results:Rs1044598 mutant genotype AA decreased the risk of ASD by 36% compared with wild genotype TT. The luciferase reporter assay further confirmed that the significant differences were detected in cotransfected plasmid (rs1044598) with miR-4252 in HEK293T,H9C2 and cardiac cells from newborn SD rats cell lines(all P < 0.05). Conclusion:Rs1044598 may be a new independent susceptibility locus of ASD. MiR-4252 down-regulates COL6A2 expression by binding to 3′-UTR of COL6A2,and rs1044598 could influence the procedure and decrease the risk of ASD.