Interaction of polymorphisms in the CARD15 and CD14 genes in patients with Crohn disease.
BACKGROUND
Associations of variations in the CARD15 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC) and Crohn disease (CD) have been shown recently. These variations are neither necessary nor sufficient for the genetic predisposition of CD. Further genetic and environmental factors play a crucial role in the pathogenesis of CD.


METHODS
To evaluate putative interactions between the CARD15 and CD14 genes in CD, a functionally relevant polymorphism in the promoter region (T/C at position -159) has been genotyped for 650 healthy controls and 253 patients with CD by RFLP analyses. CD patients were genotyped for the variations of the CARD15 gene.


RESULTS
T allele and TT genotype frequencies of the CD14 promoter were significantly increased only in CD patients with at least one variation in the CARD15 gene compared to controls (P = 0.02 and 0.0002, respectively). No significant association was found in CD patients without any of the variations.


CONCLUSIONS
Interactions of the CARD15 and CD14 genes, both of which are involved in the recognition of lipopolysaccharides, increase the risk for developing CD.
Klein
W
W
Abteilung für Humangenetik, Ruhr-Universität, Bochum, Germany. wolfram.klein@ruhr-uni-bochum.de
Tromm
A
A
Griga
T
T
Folwaczny
C
C
Hocke
M
M
Eitner
K
K
Marx
M
M
Duerig
N
N
Epplen
J T
JT
D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D004843:Epistasis, Genetic; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein