Genetic Variants of microRNA Sequences and Susceptibility to Sepsis in Patients With Major Blunt Trauma. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Zhang, An-qiang; Gu, Wei; Zeng, Ling; Zhang, Lian-yang; Du, Ding-yuan; Zhang, Mao; Hao, Jiang; Yue, Cai-li; Jiang, Jianxin
• Is Part Of: Annals of surgery. Volume 261:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000000687
• Languages: English
• ISSNs: 0003-4932

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>The objective of this study was to conduct a systematic survey of common precursor microRNA (pre-miRNA) single nucleotide polymorphisms (SNPs) and evaluate their clinical relevance in patients with major blunt trauma.</p> </sec> <sec> <title>Background:</title> <p>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.</p> </sec> <sec> <title>Methods:</title> <p>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 (1 screening cohort, n = 666) and 2 independent validated cohorts (n = 286 and n = 316, respectively) in China.</p> </sec> <sec> <title>Results:</title> <p>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 sepsis 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 anti-inflammatory cytokines. In vitro experiments further indicated that the G→C variant of this polymorphism could significantly increase the expression of mature miR-608.</p> </sec> <sec> <title>Conclusions:</title> <p>Our results indicate that the rs4919510G/C SNP in hsa-mir-608 may be a prognostic biomarker for sepsis in patients with major trauma. Further characterization of miRNA SNPs may open new avenues for studying sepsis and developing novel therapeutic approaches.</p> </sec> </abstract>