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Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143378/
https://www.ncbi.nlm.nih.gov/pubmed/34040631
http://dx.doi.org/10.3389/fgene.2021.640859
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author 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
author_facet 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
author_sort Yang, Qi
collection PubMed
description 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.
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spelling pubmed-81433782021-05-25 Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis 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 Front Genet Genetics 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. Frontiers Media S.A. 2021-04-16 /pmc/articles/PMC8143378/ /pubmed/34040631 http://dx.doi.org/10.3389/fgene.2021.640859 Text en Copyright © 2021 Yang, Pu, Li, Shi, Chen, Zhang, Hu, Zhou, Chen, Li, Tong, Férec, Cooper, Chen and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
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
Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title_full Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title_fullStr Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title_full_unstemmed Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title_short Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
title_sort digenic inheritance and gene-environment interaction in a patient with hypertriglyceridemia and acute pancreatitis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143378/
https://www.ncbi.nlm.nih.gov/pubmed/34040631
http://dx.doi.org/10.3389/fgene.2021.640859
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