Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 26:11:7.
doi: 10.3389/fgene.2020.00007. eCollection 2020.

Integration Analysis of m6A-SNPs and eQTLs Associated With Sepsis Reveals Platelet Degranulation and Staphylococcus aureus Infection are Mediated by m6A mRNA Methylation

Xuri Sun  1   2 , Yishuang Dai  3 , Guoliang Tan  1   2 , Yuqi Liu  1   2 , Neng Li  4
Affiliations

Integration Analysis of m6A-SNPs and eQTLs Associated With Sepsis Reveals Platelet Degranulation and Staphylococcus aureus Infection are Mediated by m6A mRNA Methylation

Xuri Sun et al. Front Genet. .

Abstract

Sepsis is a major threat with high mortality rate for critically ill patients. Response to pathogen infection by the host immune system is a key biological process involved in the onset and development of sepsis. Heterogeneous host genome variation, especially single nucleotide polymorphisms (SNPs), has long been suggested to contribute to differences in disease progression. However, the function of SNPs located in non-coding regions remains to be elucidated. Recently, m6A mRNA modification levels were revealed to differ at SNPs. As m6A is a crucial regulator of gene expression, these SNPs might control genes by changing the m6A level on mRNA. To investigate the potential role of m6A SNPs in sepsis, we integrated m6A-SNP and expression quantitative trait loci (eQTLs) data. Analysis revealed 15,720 m6A-cis-eQTLs and 381 m6A-trans-eQTLs associated with sepsis. We identified 1321 genes as locations of m6A-cis-eQTLs. These were enriched in platelet degranulation and Staphylococcus aureus infection pathways, which are vital for the pathophysiological process of sepsis. We conclude that m6A modification of mRNA plays a very important role in sepsis, with m6A-cis-eQTLs potentially having the most effect on individual variation in sepsis progression.

Keywords: M6A; Staphylococcus aureus; eQTL; methylation; sepsis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Manhattan plot of genome‐wide identified m6A-eQTLs in sepsis patients. The Manhattan plot displayed −log10 (p values) for each of m6A-eQTLs associated with sepsis. (A) m6A-cis-eQTLs (B) m6A-trans-eQTLs.
Figure 2
Figure 2
GO enrichment analysis displayed genes respond to m6A-cis-eQTLs are enriched in various biological processes (BP), molecular function (MF) and cellular component (CC). Note that platelet degranulation (BP) and platelet alpha granule lumen (CC) are significant pathway.
Figure 3
Figure 3
KEGG analysis revealed genes respond to m6A-cis-eQTLs are enriched diverse pathways. Note that Staphylococcus aureus infection pathway is with high significance.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alarcon C. R., Lee H., Goodarzi H., Halberg N., Tavazoie S. F. (2015). N6-methyladenosine marks primary microRNAs for processing . Nature 519 (7544), 482–485. 10.1038/nature14281 - DOI - PMC - PubMed
    1. Alvarez-Estrada A., Rodriguez-Ferri E. F., Martinez-Martinez S., Alvarez B., Fernandez-Caballero T., Dominguez J., et al. (2019). TLR2, Siglec-3 and CD163 expressions on porcine peripheral blood monocytes are increased during sepsis caused by Haemophilus parasuis . Comp. Immunol. Microbiol. Infect. Dis. 64, 31–39. 10.1016/j.cimid.2019.02.001 - DOI - PubMed
    1. Arcagok B. C., Karabulut B. (2019). Platelet to lymphocyte ratio in neonates: a predictor of early onset neonatal sepsis . Mediterr. J. Hematol. Infect. Dis. 11 (1), e2019055. 10.4084/mjhid.2019.055 - DOI - PMC - PubMed
    1. Assinger A., Schrottmaier W. C., Salzmann M., Rayes J. (2019). Platelets in sepsis: an update on experimental models and clinical data . Front. Immunol. 10, 1687. 10.3389/fimmu.2019.01687 - DOI - PMC - PubMed
    1. Avriel A., Paryente Wiessman M., Almog Y., Perl Y., Novack V., Galante O., et al. (2014). Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care . PloS One 9 (6), e100514. 10.1371/journal.pone.0100514 - DOI - PMC - PubMed