The effect of alcohol on the differential expression of cluster of differentiation 14 gene, associated pathways, and genetic network.
paper
Cited
Public
- Authors
- Zhou, Diana X; Zhao, Yinghong; Baker, Jessica A; Gu, Qingqing; Hamre, Kristin M; Yue, Junming; Jones, Byron C; Cook, Melloni N; Lu, Lu
- Year
- 2017
- Journal
- PloS one
- PMID
- 28575045
- DOI
- 10.1371/journal.pone.0178689
- PMCID
- PMC5456352
Alcohol consumption affects human health in part by compromising the immune system. In this study, we examined the expression of the Cd14 (cluster of differentiation 14) gene, which is involved in the immune system through a proinflammatory cascade. Expression was evaluated in BXD mice treated with saline or acute 1.8 g/kg i.p. ethanol (12.5% v/v). Hippocampal gene expression data were generated to examine differential expression and to perform systems genetics analyses. The Cd14 gene expression showed significant changes among the BXD strains after ethanol treatment, and eQTL mapping revealed that Cd14 is a cis-regulated gene. We also identified eighteen ethanol-related phenotypes correlated with Cd14 expression related to either ethanol responses or ethanol consumption. Pathway analysis was performed to identify possible biological pathways involved in the response to ethanol and Cd14. We also constructed a genetic network for Cd14 using the top 20 correlated genes and present several genes possibly involved in Cd14 and ethanol responses based on differential gene expression. In conclusion, we found Cd14, along with several other genes and pathways, to be involved in ethanol responses in the hippocampus, such as increased susceptibility to lipopolysaccharides and neuroinflammation.
Differential expression of the Cd14 gene across mouse strains rank ordered by expression levels.The standard deviation and mean expression of Cd14 in each mouse is shown across the parent DBA/2J and C57BL/6J strains, F1 hybrids, and 67 BXD strains. The x-axis represents the mouse strain, with the y-axis as the mean gene expression using the log2 scale.
Interval mapping for Cd14 was done using the Affymetrix dataset to identify significant eQTLs in the mouse genome.The x-axis denotes a position on the mouse genome, in megabases (Mb), while the y-axis gives the likelihood ratio statistic scores (LRS), a measurement of the linkage between differences in Cd14 and differences in the region of the genome. The blue lines indicate the LRS values at a given position, with a significant LRS at 16.56 and suggestive LRS at 10.39. There was a significant eQTL on chromosome 18, around 36β37 Mb, and a suggestive eQTL on chromosome 13.
The gene network of Cd14.The 20 genes showed significant functional cohesion with a literature p value of8.10365e-17. Each node represents a gene, and each line between genes represents the cosine score of Latent Semantic Indexing (LSI), which is the functional coherence of gene sets.
Gene expressions for Cd14, Ly86, Cd68 and Il18 in the ethanol and saline treated hippocampus were detected by quantitative RT-PCR.Data were presented in relative expression level averaged from all 10 strains in ethanol and saline treated mice (*p<0.05, **p<0.01).
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| Name | Type |
|---|---|
| 10 strains | cohort |
| 2,2,2-tribromoethanol local | drug |
| acute withdrawal | phenotype |
| Adaptive immune response local | phenotype |
| addiction | phenotype |
| adipogenesis | phenotype |
| adipokines | drug |
| Adipose tissue inflammation local | phenotype |
| Adipose tissue inflammatory activity local | phenotype |
| Affymetrix dataset local | cohort |
| Agilent 2100 Bioanalyzer | drug |
| AIF1 | gene |
| alcohol | phenotype |
| Alcohol Exposure | phenotype |
| alcohol-related behaviors | phenotype |
| alcohol sensitivity | phenotype |
| Alcohol Use Disorder | phenotype |
| Alzheimer's disease | phenotype |
| Alzheimerβs disease | phenotype |
| Anxiety phenotypes local | phenotype |
| AP1 local | gene |
| apoptosis | phenotype |
| Apoptotic process local | phenotype |
| Avertin local | drug |
| B Cell Receptor Signaling Pathway local | phenotype |
| behaviors related to ethanol local | phenotype |
| brain damage | phenotype |
| Brain inflammation local | phenotype |
| Burn injury local | phenotype |
| BXD13 local | cohort |
| BXD28 local | cohort |
| BXD family local | cohort |
| BXD mice | cohort |
| BXD phenotype database local | cohort |
| BXD RI mice local | cohort |
| BXD RI strains local | cohort |
| BXD RI strains (first set, 67 strains) local | cohort |
| BXD RI strains (second set, 26 strains) local | cohort |
| BXDs local | cohort |
| BXD strains local | cohort |
| C57BL/6J | cohort |
| Cd14 | gene |
| CD14ALL local | gene |
| Cd14 exonic SNP local | variant |
| Cd14 expression local | phenotype |
| Cd14 expression level local | phenotype |
| Cd14 SNP1 local | variant |
| Cd14 SNP2 local | variant |
| Cd14 SNP3 local | variant |
| CD68 | gene |
| Chemokine cascade local | phenotype |
| chemokine signaling pathway local | phenotype |
| chronic alcoholic liver disease local | phenotype |
| chronic alcoholism | phenotype |
| cortex | anatomy |
| CSF3 | gene |
| Cst3 | gene |
| cytokine receptor binding local | phenotype |
| D2 mice local | cohort |
| DBA2/J local | cohort |
| DBA/2J | cohort |
| Dendritic cells local | phenotype |
| dentate gyrus | anatomy |
| Embryonic neurocellular death local | phenotype |
| eQTLGen Consortium | cohort |
| Ethanol conditioned taste aversion local | phenotype |
| ethanol consumption | phenotype |
| Ethanol-induced anxiety local | phenotype |
| Ethanol-induced brain changes local | phenotype |
| Ethanol-induced locomotion local | phenotype |
| Ethanol-related phenotype local | phenotype |
| Ethanol-treated mice local | cohort |
| gene expression | phenotype |
| G protein signaling pathways local | phenotype |
| Granulocytes local | phenotype |
| heavy drinking | phenotype |
| hippocampus | anatomy |
| human alcoholics | phenotype |
| IL-1 | drug |
| IL1 local | gene |
| IL18 | gene |
| IL-6 | drug |
| IL6 | gene |
| Illumina NOE local | cohort |
| Illumina NOS local | cohort |
| IL-Signaling Pathways local | phenotype |
| immune function | phenotype |
| immune response | phenotype |
| immune system processes local | phenotype |
| inbred strains | cohort |
| inflammation | phenotype |
| inflammation of adipose tissue local | phenotype |
| Inflammatory damage local | phenotype |
| Inflammatory markers local | phenotype |
| inflammatory response | phenotype |
| Innate immune response local | phenotype |
| insulin resistance | phenotype |
| Interleukin-18 local | drug |
| Intestinal inflammation local | phenotype |
| IRAK | gene |
| kidney function | phenotype |
| lipopolysaccharide binding local | phenotype |
| Lipopolysaccharides local | drug |
| Liver inflammation local | phenotype |
| Locomotor stimulation following exposure to alcohol local | phenotype |
| LPS | drug |
| Lung inflammation local | phenotype |
| LY86 local | gene |
| macrophage activation local | phenotype |
| Macrophage apoptosis local | phenotype |
| macrophage markers local | phenotype |
| MAPK | gene |
| MAPK signaling pathway local | phenotype |
| mice | cohort |
| microglial activation | phenotype |
| midbrain | anatomy |
| Mid-brain local | anatomy |
| Moderate alcohol intake local | phenotype |
| Monocyte apoptosis local | phenotype |
| Monocyte survival local | phenotype |
| Nanodrop | drug |
| neocortex | anatomy |
| neurodegeneration | phenotype |
| neurodegenerative diseases | phenotype |
| neuroinflammation | phenotype |
| Neutrophil infiltration local | phenotype |
| NF-ΞΊB | gene |
| Niemann-Pick disease type A local | phenotype |
| Niemann-Pick disease type B local | phenotype |
| Null mutant mice local | cohort |
| obesity | phenotype |
| orbitofrontal cortex | anatomy |
| p38 MAPK | gene |
| prefrontal cortex | anatomy |
| Programmed cell death local | phenotype |
| proinflammatory cascades local | phenotype |
| Proinflammatory cytokine local | phenotype |
| Proinflammatory cytokines local | drug |
| rats | cohort |
| response to chemical stimulus local | phenotype |
| RI strains of mice local | cohort |
| RNA STAT-60 local | drug |
| saline | drug |
| Smpd1 | gene |
| striatum | anatomy |
| T Cell Receptor Signaling Pathway local | phenotype |
| tert-pentyl alcohol local | drug |
| TGF-Ξ² | drug |
| Tlr2 | gene |
| TLR3 local | gene |
| Tlr4 | gene |
| TNF-Ξ± | drug |
| TNFΞ± | drug |
| Toll-like receptors local | gene |
| toll-like receptor signaling pathways local | phenotype |
| ventral tegmental area | anatomy |
| Ξ²-actin | gene |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells? | 2018 | 29897633 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Atad1 Is a Potential Candidate Gene for Prepulse Inhibition. | Bajpai AK et al. | β | 2025 | β |
| Circular RNA RORΞ² regulates TGFΞ²R1 in alcohol-induced fibroblast-to-myofibroblast differentiation. | Sueblinvong V et al. | β | 2025 | β |
| Molecular Mechanisms Linking Genes and Vitamins of the Complex B Related to One-Carbon Metabolism in Breast Cancer: An In Silico Functional Database Study. | GΓ‘lvez-Navas JM et al. | β | 2024 | β |
| A systems genetics approach to revealing the <i>Pdgfb</i> molecular network of the retina. | Li S et al. | β | 2020 | β |
| Decoding the transcriptional programs activated by psychotropic drugs in the brain. | Zygmunt M et al. | β | 2019 | β |
| Genetic Influences on the Amount of Cell Death in the Neural Tube of BXD Mice Exposed to Acute Ethanol at Midgestation. | ThΓ©berge ET et al. | β | 2019 | β |
| Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells? | Prytkova I et al. | β | 2018 | β |