Association between the promoter polymorphism T/C at position -159 of the CD14 gene and anti-inflammatory therapy in patients with inflammatory bowel disease.
Immune response to intestinal bacteria and genetic predisposition seem to play a crucial role in the pathogenesis of inflammatory bowel disease. A single nucleotide polymorphism in the promoter of the lipopolysaccharide-receptor CD14 gene (T/C at position -159) has recently been described. To evaluate the role of the CD14 gene in anti-inflammatory therapy, the functionally relevant T(-159)-->C promoter polymorphism has been genotyped in 72 patients with inflammatory bowel disease and associated with the cumulative steroid dose. Cumulative corticosteroid dose was significantly higher in ulcerative colitis patients with the TT genotype (2447.7 +/- 927.0 mg/yr) compared with the CT genotype (142.3 +/- 142.3 mg/yr, p=0.016) and the CC genotype (391.7 +/- 272.7 mg/yr, p=0.047). In contrast, in patients with Crohn's disease there was no significant difference of the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14 genotypes. An altered immune response to lipopolysaccharides with influence on the anti-inflammatory therapy seems to play a role in the genetic predisposition to ulcerative colitis. Genetic stratification will lead to the development of individualized therapies in inflammatory bowel disease.
Griga
T
T
Department of Gastroenterology, University Hospital Bergmannsheil, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. thomas.griga@ruhr-uni-bochum.de
Wilkens
C
C
Schmiegel
W
W
Folwaczny
C
C
Hagedorn
M
M
Duerig
N
N
Epplen
J
J
Klein
W
W
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics
D000305:Adrenal Cortex Hormones; D018950:Lipopolysaccharide Receptors