Single-Nucleotide Polymorphisms in Exonic and Promoter Regions of Transcription Factors of Second Heart Field Associated with Sporadic Congenital Cardiac Anomalies.

Multiple second heart field (SHF) transcription factors are involved in cardiac development. In this article we evaluate the relationship between SHF transcription factor polymorphisms and congenital heart disease (CHD). Ten polymorphisms were used for genotyping, and three of these were used for the luciferase assay. The risk of CHD was increased 4.31 times and 1.54 times in the C allele of : rs6061243 G>C and G allele of : rs336283 A>G, respectively. The minor alleles of : rs1542088 T>G, : rs80043958 A>G and : rs6587239 T>C increased the risk of the simple types of CHD. The minor alleles of : rs41305803 G>A and : rs304154 A>G increased the risk of tetralogy of Fallot (TOF). The minor alleles of : rs336284 A>G and : rs88387557 T>G only increased the risk of a single ventricle (SV). Luciferase assays revealed that the minor alleles of rs304154 and rs336284 decreased the transcriptional levels of and respectively (p<0.01). When combined with , the G promoter showed a higher expression level than the A promoter in rs80043958 (p<0.01). Our findings suggest that minor alleles of SNPs in the exonic and promoter regions of transcription factors in the SHF can increase the risks of sporadic CHD.