Abstract
MicroRNA-146a (miR-146a) acts as a pivotal regulatory molecule in immune response and various diseases, such as carcinoma and autoimmune diseases. Growing evidences have demonstrated the association of miR-146a gene single-nucleotide polymorphisms (SNPs) with risk of several diseases, but no genetic relevance studies of miR-146a gene polymorphisms to sepsis have been reported by now. Our study has analyzed the association of sepsis with two functional miR-146a gene SNPs rs2910164 G/C and rs57095329 A/G in a Chinese Han population (226 sepsis cases; 206 healthy controls). Our results indicated a higher prevalence of the miR-146a gene SNP rs2910164 C allele and CC genotype in patients with severe sepsis (rs2910164G versus rs2910164C: P = 0.0029, odds ratio (OR) = 1.664; GG+GC versus CC: P = 0.0045, OR = 1.947). Neither the genotype nor the allele in rs57095329 showed significant differences between the septic cases and the controls (P = 0.5901 and 0.3580, resp.), and no significant difference was observed in the subgroups. In addition, we confirmed that the two SNPs rs2910164 and rs57095329 could functionally affect the miR-146a expression levels and the reduction of miR146a was accompanied with the upregulation of the expression levels of TRAF-6 and IRAK-1 in severe sepsis patients. This present study might provide valuable clinical evidence that miR-146a gene polymorphism rs2910164 is associated with the risk of severe sepsis.
Highlights
Sepsis is a systemic disease characterized by microbial infection and systemic inflammatory response syndrome (SIRS), which has high morbidity and mortality rates in Intensive Care Units (ICUs) [1]
One of these conserved miRNAs is miR-146a, which is well known for its important regulation of the immune response and inflammation [16]. miR-146a is induced upon the activation of toll-like receptor 4 (TLR4) in the NF-κB-dependent signaling pathway, leading to the downregulation of IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) [17]
Patients that were younger than 18 years old and patients who suffered from diabetes, autoimmune diseases, malignancies, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS) or receiving immunosuppressive, steroid, or radiation therapy were excluded from this study
Summary
Sepsis is a systemic disease characterized by microbial infection and systemic inflammatory response syndrome (SIRS), which has high morbidity and mortality rates in Intensive Care Units (ICUs) [1]. A number of evidences have demonstrated that functional genetic variants within genes involved in the innate and adaptive immune responses play a pivotal role in a patient’s predisposition to sepsis and their prognosis [6,7,8,9,10,11,12,13]. Many studies have identified miRNAs as vital regulatory molecules that may be involved in the pathogenesis of immune and inflammatory pathologies in human diseases [15]. One of these conserved miRNAs is miR-146a, which is well known for its important regulation of the immune response and inflammation [16]. Recent studies have demonstrated that the serum or plasma levels of miR-146a in septic patients were significantly decreased compared to those of normal controls and SIRS
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