A MIF haplotype is associated with the outcome of patients with severe sepsis: a case control study.
BACKGROUND
Macrophage 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.


METHODS
Genotype 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.


RESULTS
Genotype 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).


CONCLUSIONS
The 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.
Lehmann
Lutz E
LE
University Department of Anaesthesiology and Pain Therapy, Inselspital, CH-3010 Bern, Switzerland. lutz.lehmann@insel.ch
Book
Malte
M
Hartmann
Wolfgang
W
Weber
Stefan U
SU
Schewe
Jens-Christian
JC
Klaschik
Sven
S
Hoeft
Andreas
A
Stüber
Frank
F
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D018805:Sepsis / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
D008263:Macrophage Migration-Inhibitory Factors