Gene–environment interaction between APOA5 c.553G>T and pregnancy in hypertriglyceridemia-induced acute pancreatitis

• Published in: Journal of clinical lipidology Vol. 14; no. 4; pp. 498 - 506
• Main Authors: Pu, Na, Yang, Qi, Shi, Xiao-Lei, Chen, Wei-Wei, Li, Xiao-Yao, Zhang, Guo-Fu, Li, Gang, Li, Bai-Qiang, Ke, Lu, Tong, Zhi-Hui, Cooper, David N., Chen, Jian-Min, Li, Wei-Qin, Li, Jie-Shou
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.07.2020; Elsevier
• Subjects: Acute pancreatitis in pregnancy (APIP); APOA5 c.553G>T variant; Apolipoprotein A5; Gene–environment interaction; Hypertriglyceridemia-induced acute pancreatitis (HTG-AP); Life Sciences; Triglyceride; Hypertriglyceridemia-induced acute pancreatitis (HTG-AP); APOA5 c.553G>T variant; Gene–environment interaction; Acute pancreatitis in pregnancy (APIP); Apolipoprotein A5; Triglyceride; APOA5 c.553G> T variant
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2020.05.003

The etiology of hypertriglyceridemia (HTG) and, consequently, HTG-induced acute pancreatitis (HTG-AP), is complex. Herein, we explore a possible gene–environment interaction between APOA5 c.553G>T (p.185Gly>Cys, rs2075291), a common variant associated with altered triglyceride levels, and pregnancy in HTG-AP. We enrolled 318 Chinese HTG-AP patients and divided them into 3 distinct groups: Group 1, male patients (n = 183); Group 2, female patients whose disease was unrelated to pregnancy (n = 105); and Group 3, female patients whose disease was related to pregnancy (n = 30). APOA5 rs2075291 genotype status was determined by Sanger sequencing. A total of 362 healthy Han Chinese subjects were used as controls. Data on body mass index, peak triglyceride level, age of disease onset, episode number, and clinical severity of HTG-AP were collected from each patient. Multiple comparisons, between patient groups, between patient groups and controls, or within each patient group, were performed. A robust association of APOA5 rs2075291 with HTG-AP in general, and HTG-AP during pregnancy in particular, was demonstrated. The minor T allele showed a stronger association with Group 3 patients than with either Group 1 or Group 2 patients. This stronger association was due mainly to the much higher frequency of TT genotype in Group 3 patients (20%) than that (<6%) in Group 1 and Group 2 patients. Moreover, the TT genotype was associated with a significantly higher peak triglyceride level in Group 3 patients compared with the GG genotype. Our findings provide evidence for an interaction between APOA5 rs2075291 and pregnancy in HTG-AP. •APOA5 c.553G>T has been previously associated with altered triglyceride levels.•Here, we report for the first time an association of APOA5 c.553G>T with hypertriglyceridemia-induced acute pancreatitis (HTG-AP).•We provide evidence that APOA5 c.553G>T interacts with pregnancy in causing HTG-AP.•Our findings provide novel insights into the complex etiology of HTG-AP.