Genomic variations within matrix metalloproteinase-9 and severe sepsis

Introduction

Sepsis is a multiple-gene disease resulting from the interaction of environmental and genetic components. Matrix metalloproteinase-9 (MMP-9) has been demonstrated to play an important role in organ dysfunction and outcome of sepsis [1–3]. However, genetic predisposition of MMP-9 to sepsis remained unknown.

Methods

Seven common SNPs within the functional regions of MMP-9 gene (rs17576, rs2274756, rs2250889, rs9509, rs3918240, rs3918241 and rs3918242) were investigated in 192 patients with severe sepsis and 262 healthy controls. Meanwhile, the plasma levels of MMP-9 were measured via ELISA.

Results

The genotype distributions and allelic frequencies of the above seven SNPs were not significantly different between patients with severe sepsis and controls, as well as between surviving and nonsurviving patients with severe sepsis (all P > 0.05). Haplotype GGCTTTC, AGGTCTC, GGCCTTC, GACTTAT and AGCCCTC are the five most common haplotypes. The distribution of the haplotypes was also comparable among the defined groups. The median plasma levels of MMP-9 was 37.66 ng/ml in 32 patients within the first 24 hours following the diagnosis of severe sepsis, and 30.15 ng/ml in 19 healthy controls. Compared with those in surviving patients with severe sepsis (median 37.66 ng/ml, n = 16) and healthy controls, the concentrations of MMP-9 appeared an increasing trend in nonsurviving patients with severe sepsis (median 36.06 ng/ml, n = 16).

Conclusion

The present findings suggest that common polymorphisms within the function regions of MMP-9 gene may not play a major role in the predisposition to severe sepsis in the Chinese Han cohort. The plasma levels of MMP-9 may associate with the outcome of severe sepsis. Further studies in large samples need to be guaranteed.