• Annals of surgery · Jan 2015

    Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.

    • An-qiang Zhang, Wei Gu, Ling Zeng, Lian-yang Zhang, Ding-yuan Du, Mao Zhang, Jiang Hao, Cai-li Yue, and Jianxin Jiang.
    • *State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China †Chongqing Emergency Medical Center, Chongqing, China ‡The Second Affiliated Hospital, Zhejiang University, Zhejiang, China §Kunming General Hospital, Chengdu Military of PLA, Yunnan, China.
    • Ann. Surg.. 2015 Jan 1;261(1):189-96.

    ObjectiveThe 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.BackgroundRecent 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.MethodsWe 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.ResultsAmong 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.ConclusionsOur 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.

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