Pathogenic analysis of apolipoprotein A5 gene variants in patients with hypertriglyceridemia-associated acute pancreatitis
10.3760/cma.j.cn115667-20241101-00181
- VernacularTitle:载脂蛋白A5基因突变在高三酰甘油血症性急性胰腺炎患者中的致病性分析
- Author:
Na PU
1
;
Qi YANG
1
;
Gang LI
1
Author Information
1. 中国人民解放军东部战区总医院（南京大学医学院附属金陵医院）重症医学科，南京 210000
- Publication Type:Journal Article
- Keywords:
Acute pancreatitis, hypertriglyceridemia;
Apolipoproteins A;
Gene mutation
- From:
Chinese Journal of Pancreatology
2025;25(1):16-23
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the distribution features and pathogenicity of apolipoprotein A5 (APOA5) gene variants in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP).Methods:Clinical data of 495 patients with HTG-AP in severe acute pancreatitis center of Eastern Theater General Hospital were collected. Next generation sequencing was performed to analyze the whole exonic regions to screen APOA5 gene variants in patients with HTP-AP. Sanger sequencing was used for validation. Bioinformative methods including mutation search, conservative analysis and pathogenicity were used to predict the functions of related mutations. 3D structural modeling were further used to evaluate the structure and function of potential mutated protein. Results:Of 495 HTG-AP patients, 275 patients (55.78%) carried APOA5 exomic variants, including 2 common missense polymorphisms as c.457G>A (100 heterozygotes and 13 homozygotes, with a prevalence of 22.83%), and c.553G>T (111 heterozygotes and 31 homozygotes, with a prevalence of 28.69%), as well as 13 rare APOA5 variants (all heterozygotes). In particular, 62 cases of enrolled patients were those suffering acute pancreatitis in pregnancy (APIP), and among them 37 carriers (58.06%) of APOA5 variants were found. Furthermore, 25(67.57%) of the APIPs carrying c.553G>T missense polymorphism, and among them 1 patient was compound with a novel APOA5 frame-shift variant c.230dupT (p.S78Efs). As bioinformatics predicted, the frame-shift variant c.230dupT was probably pathogenic and missense variant c.553G>T had potential pathogenecity, whereas the 3D-modeling of protein structure suggested that the p.Ser78fs shifting was clearly loss-of-function (LoF), and the p.Gly185Cys substitution was potential LoF. Conclusions:The current study indicates that prevalence of APOA5 gene deficiency is found in HTG-AP patients, and the interaction between APOA5 gene deficiency and pregnancy plays an important role in the development and recurrence of HTG-APIP.
