Sun Xuri, Dai Yishuang, Tan Guoliang, Liu Yuqi, Li Neng
Department of Critical Care Medicine, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
Respiratory Medicine Center of Fujian Province, Quanzhou, China.
Front Genet. 2020 Feb 26;11:7. doi: 10.3389/fgene.2020.00007. eCollection 2020.
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, mA mRNA modification levels were revealed to differ at SNPs. As mA is a crucial regulator of gene expression, these SNPs might control genes by changing the mA level on mRNA. To investigate the potential role of mA SNPs in sepsis, we integrated mA-SNP and expression quantitative trait loci (eQTLs) data. Analysis revealed 15,720 mA-cis-eQTLs and 381 mA-trans-eQTLs associated with sepsis. We identified 1321 genes as locations of mA-cis-eQTLs. These were enriched in platelet degranulation and infection pathways, which are vital for the pathophysiological process of sepsis. We conclude that mA modification of mRNA plays a very important role in sepsis, with mA-cis-eQTLs potentially having the most effect on individual variation in sepsis progression.
脓毒症是重症患者面临的主要威胁，死亡率很高。宿主免疫系统对病原体感染的反应是脓毒症发生和发展过程中涉及的关键生物学过程。长期以来，人们一直认为宿主基因组的异质性变异，尤其是单核苷酸多态性（SNP），会导致疾病进展的差异。然而，位于非编码区的SNP的功能仍有待阐明。最近，研究发现SNP处的mA mRNA修饰水平存在差异。由于mA是基因表达的关键调节因子，这些SNP可能通过改变mRNA上的mA水平来控制基因。为了研究mA SNP在脓毒症中的潜在作用，我们整合了mA-SNP和表达定量性状位点（eQTL）数据。分析发现了15720个与脓毒症相关的mA顺式eQTL和381个mA反式eQTL。我们确定了1321个基因作为mA顺式eQTL的位置。这些基因在血小板脱颗粒和感染途径中富集，而这些途径对脓毒症的病理生理过程至关重要。我们得出结论，mRNA的mA修饰在脓毒症中起着非常重要的作用，其中mA顺式eQTL可能对脓毒症进展的个体差异影响最大。
