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, 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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Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00571-0 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Li Hua ◽

Quanhua Liu ◽

Jing Li ◽

Xianbo Zuo ◽

Qian Chen ◽

...

Keyword(s):

Environmental Factors ◽

Cord Blood ◽

Synergistic Effects ◽

Gene Interaction ◽

Independent Effect ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Gene Environment Interaction ◽

Gene Environment

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

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

Journal of Clinical Lipidology ◽

10.1016/j.jacl.2020.05.003 ◽

2020 ◽

Vol 14 (4) ◽

pp. 498-506

Author(s):

Na Pu ◽

Qi Yang ◽

Xiao-Lei Shi ◽

Wei-Wei Chen ◽

Xiao-Yao Li ◽

...

Keyword(s):

Acute Pancreatitis ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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Biometric and developmental gene–environment interactions: Looking back, moving forward

Development and Psychopathology ◽

10.1017/s0954579407000478 ◽

2007 ◽

Vol 19 (4) ◽

pp. 961-976 ◽

Cited By ~ 46

Author(s):

James Tabery

Keyword(s):

Complex Traits ◽

Environment Interaction ◽

Developmental Gene ◽

Statistical Interaction ◽

Gene Environment Interaction ◽

History Of Research ◽

Gene Environment ◽

Lancelot Hogben ◽

History Of ◽

Looking Back

AbstractA history of research on gene–environment interaction (G × E) is provided in this article, revealing the fact that there have actually been two distinct concepts of G × E since the very origins of this research. R. A. Fisher introduced what I call the biometric concept of G × E (G × EB), whereas Lancelot Hogben introduced what I call the developmental concept of G × E (G × ED). Much of the subsequent history of research on G × E has largely consisted of the separate legacies of these separate concepts, along with the (sometimes acrimonious) disputes that have arisen time and again when employers of each have argued over the appropriate way to conceptualize the phenomenon. With this history in place, more recent attempts to distinguish between different concepts of G × E are considered, paying particular attention to the commonly made distinction between “statistical interaction” and “interactionism,” and Michael Rutter's distinction between statistical interaction and “the biological concept of interaction.” I argue that the history of the separate legacies of G × EB and G × ED better supports Rutter's analysis of the situation and that this analysis best paves the way for an integrative relationship between the various scientists investigating the place of G × E in the etiology of complex traits.

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Behavior Genetic Approaches for Situation Research

The Oxford Handbook of Psychological Situations ◽

10.1093/oxfordhb/9780190263348.013.35 ◽

2017 ◽

pp. 24-39

Author(s):

Daniel A. Briley

Keyword(s):

Environmental Variables ◽

Behavior Genetics ◽

Behavioral Genetics ◽

Situational Factors ◽

Environment Interaction ◽

Selection Effects ◽

Personality Psychology ◽

Gene Environment Interaction ◽

Gene Environment ◽

History Of

As a field, behavior genetics has a long and often underappreciated focus on environmental and situational factors. This chapter describes the methodological details and empirical findings of this line of work, as well as what situation research can gain from behavior genetics and vice versa. Genetically informative designs offer tools to quantify the extent to which people actively create their situational experiences as opposed to randomly encountering them, and novel advances in situation research have the potential to clarify the scattered history of environmental variables in behavioral genetics. Current progress in personality psychology will be highlighted. Parallels between behavior genetics and personality work can be found both in terms of mechanisms (e.g., gene-environment correlation and gene × environment interaction contrasting with selection effects and person × situation effects) and explanatory pitfalls. Researchers interested in delineating the pathways from situations to behavior would do well to draw from and build upon work in behavior genetics.

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Elementary, my dear Watson, the clue is in the genes…or is it?

Proceedings of the British Academy, Volume 117 ◽

10.5871/bacad/9780197262795.003.0016 ◽

2003 ◽

Author(s):

ANNETTE KARMILOFF-SMITH

Keyword(s):

Regulation Of Gene Expression ◽

Gene Interaction ◽

Developmental Time ◽

Vital Role ◽

Adult Brain ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment ◽

Infant Brain ◽

The Brain

This chapter argues that there is no one-to-one, direct mapping between specific sets of genes and cognitive-level outcomes. Rather, there are very indirect mappings, with the regulation of gene expression more likely to contribute to very broad differences in developmental timing, neuronal type, neuronal density, firing thresholds, neurotransmitter types, etc. It presents the neuroconstructivist framework where gene/gene interaction, gene/environment interaction and, crucially, the process of ontogeny itself (pre- and postnatal development) are all considered to play a vital role in how genes are expressed and how the brain progressively sculpts itself, slowly becoming specialised over developmental time. The infant brain is not simply a miniature version of the adult brain.

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