Intronic Polymorphisms in Gene of Second Heart Field as Risk Factors for Human Congenital Heart Disease in a Chinese Population.

Transcriptional factors and signaling factors in the second heart field (SHF) contribute to cardiac development. However, the associations of intronic gene variants in the SHF with congenital heart disease (CHD) remain ununderstood. Ten single nucleotide polymorphisms (SNPs) from our previous sequencing data were selected and then genotyped in 383 CHD patients and 384 healthy controls in a Chinese population. Genotype analyses revealed that minor alleles in : rs12165908 C > G [odds ratio (OR) = 2.64; 95% confidence interval (CI) = 1.87-3.73,  = 3.03 × 10] and : rs143085291 C > T (OR = 2.49; 95% CI = 1.18-5.29,  = 0.01) increased CHD risk significantly. Meanwhile, : rs78454549 T > C and : rs13275657 A>G polymorphisms were significantly associated with increased risk of simple CHDs. The minor allele C in : rs17153694 T > C increased the risk of tetralogy of Fallot, whereas minor alleles in : rs41298006 G>A, : rs75629618 C>T, rs10461755 G>A, rs75632187 A>G, and rs12518964 G > A were associated with increased risk of single ventricle. The minor allele T in rs143085291 in enhancer decreased the transcription level in luciferase assay. Our findings suggest that intronic SNPs in transcriptional factors and signaling factors in the SHF are significantly associated with increased risk of different CHD types.