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- Title
Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis.
- Authors
Yang, Qi; Pu, Na; Li, Xiao-Yao; Shi, Xiao-Lei; Chen, Wei-Wei; Zhang, Guo-Fu; Hu, Yue-Peng; Zhou, Jing; Chen, Fa-Xi; Li, Bai-Qiang; Tong, Zhi-Hui; Férec, Claude; Cooper, David N.; Chen, Jian-Min; Li, Wei-Qin
- Abstract
The etiology of hypertriglyceridemia (HTG) and acute pancreatitis (AP) is complex. Herein, we dissected the underlying etiology in a patient with HTG and AP. The patient had a 20-year history of heavy alcohol consumption and an 8-year history of mild HTG. He was hospitalized for alcohol-triggered AP, with a plasma triglyceride (TG) level up to 21.4 mmol/L. A temporary rise in post-heparin LPL concentration (1.5–2.5 times of controls) was noted during the early days of AP whilst LPL activity was consistently low (50∼70% of controls). His TG level rapidly decreased to normal in response to treatment, and remained normal to borderline high during a ∼3-year follow-up period during which he had abstained completely from alcohol. Sequencing of the five primary HTG genes (i.e., LPL , APOC2 , APOA5 , GPIHBP1 and LMF1) identified two heterozygous variants. One was the common APOA5 c.553G > T (p.Gly185Cys) variant, which has been previously associated with altered TG levels as well as HTG-induced acute pancreatitis (HTG-AP). The other was a rare variant in the LPL gene, c.756T > G (p.Ile252Met), which was predicted to be likely pathogenic and found experimentally to cause a 40% loss of LPL activity without affecting either protein synthesis or secretion. We provide evidence that both a gene-gene interaction (between the common APOA5 variant and the rare LPL variant) and a gene-environment interaction (between alcohol and digenic inheritance) might have contributed to the development of mild HTG and alcohol-triggered AP in the patient, thereby improving our understanding of the complex etiology of HTG and HTG-AP.
- Subjects
GENOTYPE-environment interaction; GENETIC variation; HYPERTRIGLYCERIDEMIA; HEPARIN; PANCREATITIS; ALCOHOL drinking
- Publication
Frontiers in Genetics, 2021, Vol 11, pN.PAG
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2021.640859