Molecular characterization of vascular intestinal obstruction using whole-exome sequencing

BACKGROUND: Vascular intestinal obstruction is a rare intestinal disease with a rapid progression, poor prognosis, and high mortality. This study aimed to identify several mutations associated with vascular intestinal obstruction. METHODS: Whole-exome sequencing (WES) was performed on the peripheral blood of 9 sporadic patients with acute vascular intestinal obstruction. The mutation genes in each patient and the mutation genes shared by all 9 patients were identified. Next, a functional annotation analysis and a protein-protein interaction (PPI) analysis of the shared mutation genes in the 9 patients were performed. Copy number variations (CNVs) were identified using the open-source software CNV kit. RESULTS: In total, all 9 patients shared 112 mutation genes. The Reactome database revealed 2 significantly enriched pathways, the O-linked glycosylation of the mucins (MUCs), and the termination of the O-glycan biosynthesis. MUC5AC was the protein with the highest degree in the PPI network. After searching the TiGER database, the keratin 18 (KRT18), MUC4, and MUC3A genes were found to be significantly more highly expressed in the colon tissues than the other tissues. Additionally, ArfGAP with dual PH domains 1 (ADAP1), cytochrome P450 family 2 subfamily W member 1 (CYP2W1), and transmembrane protein 184A (TMEM184A) were found to be highly expressed in colon tissues. The expression levels of several candidate genes between the vascular intestinal obstruction and normal control patients were measured by quantitative real-time polymerase chain reaction (qRT-PCR). CONCLUSIONS: Our study identified multiple mutations in 4 genes (i.e., MUC3A, MUC5AC, MUC16, and KRT18), and the CYP2W1 deletion. Our findings extend understandings of the potential pathological mechanism of vascular intestinal obstruction.