The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population

Mediators Inflamm. 2014;2014:916202. doi: 10.1155/2014/916202. Epub 2014 Feb 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adult
  • Aged
  • Case-Control Studies
  • China
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic*
  • Sepsis / enzymology
  • Sepsis / genetics*
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • MIRN146 microRNA, human
  • MicroRNAs
  • TNF Receptor-Associated Factor 6
  • TRAK1 protein, human