Association Study Of Single Nucleotide Polymorphisms In Matrix Metalloproteinases-9 Gene With Severe Sepsis

Sepsis is a complex disease resulting from the interactions between the environmental factors and genetic factors.It has been anticipated that single nucleotide polymorphisms(SNPs) in genes participating in the pathophysiologic process of sepsis may contribute to the susceptibility to sepsis and the outcome of sepsis.The activity of MMP-9 was closely associated with the severity,the organ dysfunction and the prognosis of sepsis.However,the correlation between genomic variations in MMP-9 gene and severe sepsis has never been reported.The present study was designed to investigate common SNPs within the function regions of MMP-9 gene in 192 patients with severe sepsis and 262 healthy controls using direct sequencing or PCR-RFLP.Meanwhile,the plasma levels of MMP-9 in patients of severe sepsis and healthy controls were measured by means of ELISA.The allelic frequencies and genotype distributions of SNPs rs3918240,rs3918241, rs3918242,rs9509,rs17576,2274756 and rs2250889 showed no significant difference between patients with severe sepsis and controls,as well as between surviving patients with severe sepsis and non-surviving patients with severe sepsis(all p＞0.05).Five common haplotypes(GGCTTTC,AGGTCTC,GGCCTTC,GACTTAT,AGCCCTC) were estimated in the current cohort using SNPStats program.The distributions of these five haplotype between patients with severe sepsis and controls as well as between surviving patients with severe sepsis and non-surviving patients with severe sepsis were also comparable(all p＞0.05).The median plasma levels of MMP-9 in patients of severe sepsis within 24 hours after diagnosis were 37.66ng/ml,while it was 30.15ng/ml in healthy controls.Although no significant difference between these two groups,there was an increasing trends in the concentrations of plasma MMP-9 in non-surviving patients with severe sepsis when compared with controls and surviving patients with severe sepsis.The polymorphisms in MMP-9 gene were not associated with the susceptibility to and outcome of severe sepsis and may not be served as genetic markers for severe sepsis.The plasma level of MMP-9 may correlated with the outcome of severe sepsis.