Wei Gu
Third Military Medical University China
Title: Common SNP in pre-miR-608 decreases mature miR expression and predisposes to sepsis in severe trauma patients
Biography
Biography: Wei Gu
Abstract
Recent evidence indicates that small noncoding RNA molecules known as miRNAs can function as important negative gene regulators and are implicated in the pathogenesis of various diseases. We conducted a 2-stage study to examine the impact of 9 selected SNPs with potential functional significance on the susceptibility to sepsis of 1268 trauma patients in China. Among the 9 selected SNPs with potential functional significance,only 1 (miR-608 rs4919510) was found to be strongly associated with a higher risk of developing spsis and multiple organ dysfunction in all 3 independent study cohorts. An even stronger association was observed for the rs4919510 polymorphism when combining these 3 study cohorts together. In addition, the rs4919510 polymorphism showed a significant correlation with a higher production of proinflammatory cytokines and a lower production of antiinflammatory cytokines. In vitro experiments further indicated that the G→C variant of this polymorphism could significantly increase the expression of mature miR-608. Furthermore, we illustrated that miR-608 downregulated ELA2 mRNA and protein by directly binding exon of ELANE in monocytes based on expression genechip and several in vitro experiments. Our data showed that miR-608 and its target, ELA2, maybe potential biomarkers or targets of sepsis in severe trauma patients.