Analysis of lipid metabolism gene mutations and pathogenicity in patients with hypertriglyceridemia-associated acute pancreatitis
10.3760/cma.j.cn115667-20241103-00185
- VernacularTitle:高三酰甘油血症性急性胰腺炎患者的脂代谢基因突变及其致病性分析
- Author:
Qi YANG
1
;
Na PU
1
;
Yichen DUAN
1
;
Kun GAO
1
;
Jing ZHOU
1
;
Bo YE
1
;
Gang LI
1
;
Lu KE
1
;
Yuxiu LIU
1
;
Zhihui TONG
1
;
Weiqin LI
1
;
Baiqiang 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;
Gene mutation;
Lipid metabolism disorders;
Pathogenicity
- From:
Chinese Journal of Pancreatology
2025;25(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate lipid metabolism gene mutations and pathogenicity of hypertriglyceridemia acute pancreatitis (HTG-AP) patients.Methods:Clinical data of 495 HTG-AP patients admitted from June 2018 to June 2020 in the center for severe acute pancreatitis of Eastern Theater General Hospital were retrospectively analyzed. Whole-exome sequencing and mutation verification were performed by next-generation sequencing technology and Sanger sequencing. The pathogenicity of gene mutation was analyzed by population mutation ratio, pathogenicity prediction software, conservation scoring software, protein structure prediction, and in vitro experiments. Results:The mutation ratio of lipid metabolism-related genes, namely LPL, APOA5, LMF1, GPIHBP1, and APOC2, were 14.81%, 55.78%, 43.61%, 1.62%, and 0.61%, respectively. Among them, 44 heterozygous mutations in LPL gene were detected including 36 missense mutations, 5 nonsense mutations and 3 frameshift mutations, which were all rarely carried in single patient. Six HTG-AP patients carried the LPL gene heterozygous mutation c.835C>G (p.Leu279Val). The mean level of serum triglyceride at the onset of HTG-AP was 27.4 mmol/L. All of them had a history of recurrent HTG-AP, and most of them had severe acute pancreatitis. The serum LPL concentration and activity were lower than the normal level. The pathogenicity analysis results suggested that the LPL p.Leu279Val was a rare, highly possible pathogenic and highly conserved gene mutation. The in vitro results showed that the LPL p.Leu279Val could significantly reduce the synthesis and secretion ability of LPL as well as its enzymatic activity. Conclusions:The mutation ratio of lipid metabolism-related genes, including LPL, APOA5, LMF1, GPIHBP1, and APOC2, are relatively high in the HTG-AP patients. The LPL p.Leu279Val is a rare and highly possible pathogenic gene mutation, which may lead to recurrent episodes of HTG-AP.
