Abstract
BackgroundMacrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. In the promoter region a C/G single nucleotide polymorphism (SNP) at position -173 (rs755622) and a CATT5-8 microsatellite at position -794 are related to modified promoter activity. The purpose of the study was to analyze their association with the incidence and outcome of severe sepsis.MethodsGenotype distributions and allele frequencies in 169 patients with severe sepsis, 94 healthy blood donors and 183 postoperative patients without signs of infection or inflammation were analyzed by real time PCR and Sequence analysis. All included individuals were Caucasians.ResultsGenotype distribution and allele frequencies of severe sepsis patients were comparable to both control groups. However, the genotype and allele frequencies of both polymorphisms were associated significantly with the outcome of severe sepsis. The highest risk of dying from severe sepsis was detectable in patients carrying a haplotype with the alleles -173 C and CATT7 (p = 0.0005, fisher exact test, RR = 1,806, CI: 1.337 to 2.439).ConclusionThe haplotype with the combination of the -173 C allele and the -794 CATT7 allele may not serve as a marker for susceptibility to sepsis, but may help identify septic patients at risk of dying.
Highlights
Macrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis
Macrophage Migration Inhibitory Factor (MIF) is a cytokine widely expressed in both immune and nonimmune cells playing an essential role in the pathophysiology of host immune and inflammatory responses [1,2]
The aim of this study was to evaluate the association of the MIF-173 G/C single nucleotide polymorphism (SNP) and the MIF -794 CATT5-8 microsatellite with severe sepsis compared to healthy blood donors and patients with abdominal surgery but without signs of infection or inflammation
Summary
Macrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. Macrophage Migration Inhibitory Factor (MIF) is a cytokine widely expressed in both immune and nonimmune cells playing an essential role in the pathophysiology of host immune and inflammatory responses [1,2]. MIF was shown to influence immuno-regulatory processes by indirectly affecting the transcriptional activity of nuclear transcription factor AP1 [10]. Circulating concentrations of MIF were markedly elevated in children and adults who had severe sepsis or septic shock [12]. Circulating MIF levels are correlated with sepsis severity scores, presence of shock, disseminated intravascular coagulation, urine output, blood pH, and lactate and cytokine levels [12]. High levels of circulating MIF are associated with a fatal outcome [12,13]
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