title: Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *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.
authors.forename: An-qiang
authors.initials: AQ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.forename: Ling
authors.initials: L
authors.lastname: Zeng
authors.forename: Lian-yang
authors.initials: LY
authors.lastname: Zhang
authors.forename: Ding-yuan
authors.initials: DY
authors.lastname: Du
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.forename: Jiang
authors.initials: J
authors.lastname: Hao
authors.forename: Cai-li
authors.initials: CL
authors.lastname: Yue
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000235:genetics; D009104:Multiple Trauma / Q000097:blood / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics*; D014949:Wounds, Nonpenetrating / Q000097:blood / Q000150:complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; D035683:MicroRNAs