The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis

Background and aims: To study the role of gene mutations in the development of severe hypertriglyceridemia in patients with hyperlipidemic acute pancreatitis (HLAP), especially different APOA5 mutations. Methods: Whole exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The products of pathogenic mutations in APOA5 were visualized using software simulations. The clinical data of the patients were also collected and analyzed. Results: 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, p.H182fs) were positively correlated with severe hypertriglyceridemia; they were all in the important domains of apolipoprotein A-V (apoA-V). p.R223C has the potential to be one of the most deleterious mutations to apoA-V, considering the specific position of residue 223 and the altered amino acid property. 3. Four new APOA5 mutations were identified, namely c.563A>T, c.667C>T, c.788G>A and c.544_545 insGGTGC. Conclusions: The pathogenic mutations of APOA5 were specific to the HLAP patients with severe hypertriglyceridemia in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.