A polymorphism in the macrophage migration inhibitory factor gene is involved in the genetic predisposition of Crohn's disease and associated with cumulative steroid doses.
OBJECTIVE
Macrophage migration inhibitory factor (MIF) is an important cytokine involved in the regulation of the innate immune system in IBD. Secreted MIF is able to induce the production of pro-inflammatory cytokines and counteracts anti-inflammatory effects of steroids. We evaluated whether the single nucleotide polymorphism (SNP) G/C at position -173 of the MIF gene contributes to the predisposition to IBD and higher amounts of steroid therapy.


METHODS
We genotyped the SNP G/C at position -173 of the MIF gene in 157 patients with Crohn's disease (CD), 102 patients with ulcerative colitis (UC) and 489 healthy controls. Allele frequencies and cumulative steroid doses were compared.


RESULTS
C allele and CC genotype frequencies were significantly decreased in CD patients compared to controls (p < 0.012 and p < 0.022, respectively). No significant differences were found in UC patients compared to controls. Cumulative corticosteroid dose was significantly higher in CD patients with the CC genotype [12300mg/yr (0-40000mg/yr), p < 0.021] compared with the GC genotype [220mg/yr (0-450mg/yr) and the GG genotype (310mg/yr (100-500mg/yr)]. In contrast, there were no significant differences between the genotypes in UC patients.


CONCLUSIONS
Our data demonstrate the counterregulatory effects of MIF in CD patients and indicate the important role of the SNP G/C at position -173 of the MIF gene for the anti-inflammatory therapy with glucocorticoids.
Griga
Thomas
T
Department of Gastroenterology, University Hospital Bergmannsheil, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. thomas.griga@ruhr-uni-bochum.de
Wilkens
Christian
C
Wirkus
Natascha
N
Epplen
Joerg
J
Schmiegel
Wolff
W
Klein
Wolfram
W
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D013256:Steroids / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D013256:Steroids