The c.1-260C>T promoter variant of CD14 but not the c.896A>G (p.D299G) variant of toll-like receptor 4 (TLR4) genes is associated with inflammatory bowel disease.
BACKGROUND
Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest.


METHODS
In this two-center, retrospective German and Hungarian cohort study, patients with Crohn's disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed.


RESULTS
In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383).


CONCLUSIONS
IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.
Baumgart
Daniel C
DC
Division of Gastroenterology and Hepatology, Department of Medicine, Charité Medical School, Humboldt University of Berlin, Berlin, Germany. daniel.baumgart@charite.de
Buning
Carsten
C
Geerdts
Lars
L
Schmidt
Hartmut H
HH
Genschel
Janine
J
Fiedler
Thomas
T
Gentz
Enno
E
Molnar
Tomas
T
Nagy
Ferenc
F
Lonovics
Janos
J
Lochs
Herbert
H
Wiedenmann
Bertram
B
Nickel
Renate
R
Witt
Heiko
H
Dignass
Axel
A
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4