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

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 noncoding regions remains to be elucidated. Recently, m 6 A mRNA modification levels were revealed to differ at SNPs. As m 6 A is a crucial regulator of gene expression, these SNPs might control genes by changing the m 6 A level on mRNA. To investigate the potential role of m 6 A SNPs in sepsis, we integrated m 6 A-SNP and expression quantitative trait loci (eQTLs) data. Analysis revealed 15,720 m 6 A-cis-eQTLs and 381 m 6 A-trans-eQTLs associated with sepsis. We identified 1321 genes as locations of m 6 A-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 m 6 A modification of mRNA plays a very important role in sepsis, with m 6 A-cis-eQTLs potentially having the most effect on individual variation in sepsis progression.

Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury

“…Sepsis, which has a worldwide mortality rate of 10%, is induced by infection and leads to life-threatening organ dysfunction (1). Clinical and basic research have shown that the cardiovascular system is affected during sepsis (2), but the exact mechanism is not fully understood.…”

RNA m6A Modification in Immunocytes and DNA Repair: The Biological Functions and Prospects in Clinical Application

“…Last but not least, m 6 A modification is supposed to be highly relevant to gut microbiota (Jabs et al, 2020), heat shock proteins (Feng et al, 2020), sepsis (Sun et al, 2020;Xing et al, 2021), and pulmonary hypertension (Pan et al, 2020) and even peripheral nerve injury (Zhang L et al, 2021). These studies can provide valuable experimental basis for development of new treatments.…”

Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China

“…The targets related to the active compounds were screened using Swiss Target Prediction (http://www.swisstarge tprediction.ch/, accessed on 30 June 2020). DAVID 6.8 (http://david.abcc.ncifcrf.gov/, accessed on 2 July 2020) was employed for the KEGG pathway and GAD disease enrichment analyses of the targets [40,41]. According to the enrichment scores obtained from the bioinformatics analysis, the target genes associated with the "lung adenocarcinoma" disease name were collected using GeneCards (https://www.genecards.org/, accessed on 2 July 2020).…”