Bioinformatic analysis of genes and micrornas associated with atrioventricular septal defect in down syndrome patients

Abstract

Down syndrome (DS) is a common chromosome 21 abnormality disease, leading to various health problems, especially atrioventricular septal defect (AVSD). Genes and microRNAs (miRNAs) associated with AVSD in DS patients still need in-depth study. Gene expression data (GSE34457) of 22 DS patients without congenital heart disease and 7 DS patients with AVSD were downloaded from Gene Expression Omnibus. After screening differentially expressed genes (DEGs) based on limma package in R (criteria: P < 0.05 and |log2fold change (FC)| > 0.5), pathway and functional enrichment analyses were performed using the online software DAVID (criterion: P < 0.05). The protein-protein interaction (PPI) networks of DEGs were constructed based on the online server STRING (criterion: combined score > 0.4). Next, miRNAs that targeted DEGs were predicted based on Webgestalt (criteria: P < 0.05 and target DEGs ≥ 2), and miRNA-DEG regulatory networks were visualized through Cytoscape. A total of 179 DEGs were identified. Next, 5 functions and 1 pathway were enriched by up-regulated DEGs, while 4 functions were enriched by down-regulated DEGs. Furthermore, miRNA-DEG regulatory networks were constructed. IL1B was the hub-gene of PPI networks, and AUTS2 and KIAA2022 were predicted to be targeted by miR-518a, miR-518e, miR-518f, miR-528a, and miR-96. IL1B, IL12RB2, AUTS2, and KIAA2022 might participate in AVSD in DS patients, and AUTS2 and KIAA2022 might be targeted by miR-518a, miR-518e, miR-518f, miR-528a, and miR-96. The identified genes and miRNAs might provide a theoretical basis for understanding AVSD in DS patients.