1.NHC Laboratory of Congenital Malformation, Shengjing Hospital of China Medical University, Liaoning, Shenyang 110004, China; 2.Department of Ultrasound, Shengjing Hospital of China Medical University, Liaoning, Shenyang 110004, China
Abstract: 【Abstract】 Objective To screen the differential expressed microRNAs (miRNAs) in maternal serum of pregnant women with congenital heart disease (CHD) fetuses and to confirm the potential biomarkers for non-invasive prenatal diagnosis of CHD. Methods From January 2012 to December 2015, 50 pregnant women who were diagnosed as pregnant with CHD fetuses by prenatal ultrasound examination in Shengjing Hospital of China Medical University were recruited. Fifty cases of normal pregnant women whose gestational week and maternal age matched with the CHD group were selected as the control group. The high-throughput screening was used for the differential expressed microRNAs in maternal serum with CHD fetuses by miRNA microarray analysis. The differential expressed microRNAsin maternal serum were further verified by the method of real-time quantitative PCR between study group and control group. Independent sample t-test and receiver operating characteristic (ROC) curves were used for statistical analysis. Results Among the 1 033 miRNAs detected in the maternal serum by miRNA microarray analysis, 38 miRNAs showed at least a 2-fold difference between study group and control group. Bioinformatics signal pathway analysis showed that the top two pathways were adrenergic signaling pathway and AMPK signaling pathway in cardiomyocytes. The expression of 4 miRNAs (miR-3199, miR- 125b-2-3p, miR-4666a-3p and miR-4681) in CHD group was significantly lower than that in control group; the expression of 3 miRNAs (miR-3664-3p, miR-1275 and miR-4796-3p) in CHD group was significantly higher than that in control group. Conclusions The 7 differential expressed miRNAs in maternal serum of pregnant women can be used as the new biomarkers for non-invasive prenatal diagnosis of fetal CHD and has latent clinical value.