Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2017 Jun 2;12(6):e0178689.
doi: 10.1371/journal.pone.0178689. eCollection 2017.

The Effect of Alcohol on the Differential Expression of Cluster of Differentiation 14 Gene, Associated Pathways, and Genetic Network

Free PMC article
Comparative Study

The Effect of Alcohol on the Differential Expression of Cluster of Differentiation 14 Gene, Associated Pathways, and Genetic Network

Diana X Zhou et al. PLoS One. .
Free PMC article


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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Fig 1
Fig 1. 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.
Fig 2
Fig 2. 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 36–37 Mb, and a suggestive eQTL on chromosome 13.
Fig 3
Fig 3. 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.
Fig 4
Fig 4. 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).

Similar articles

See all similar articles

Cited by 2 articles


    1. Molina P, Happel K, Zhang P, Kolls J, Nelson S. Focus On: Alcohol and the Immune System. Alcohol and Health. 2010; 33(1), 97–108. - PMC - PubMed
    1. Szabo G, Saha B. Alcohol’s Effect on Host Defense. Alcohol Research: Current Reviews. 2015; 37(2): 159–170. - PMC - PubMed
    1. Messingham KA, Faunce DE, Kovacs EJ. Alcohol, injury and cellular immunity. Alcohol. 2002. l 28: 137–149. - PubMed
    1. Goral J, Karavitis J, Kovacs EJ. Exposure-dependent effects of ethanol on the innate immune system. Alcohol. 2008; 42(4): 237–247. doi: 10.1016/j.alcohol.2008.02.003 - DOI - PMC - PubMed
    1. González-Reimers E, Santonaraia-Fernández F, Martin-González MC, Fernández-Rodríguez CM, Quintero-Platt G. Alcholism: A systemic proinflammatory condition. World Journal of Gateroenterology. 2014; 20(40): 14660–1471. - PMC - PubMed

Publication types

MeSH terms