On the genetic involvement of apoptosis-related genes in Crohn's disease as revealed by an extended association screen using 245 markers: no evidence for new predisposing factors.
Crohn's disease (CD) presents as an inflammatory barrier disease with characteristic destructive processes in the intestinal wall. Although the pathomechanisms of CD are still not exactly understood, there is evidence that, in addition to e.g. bacterial colonisation, genetic predisposition contributes to the development of CD. In order to search for predisposing genetic factors we scrutinised 245 microsatellite markers in a population-based linkage mapping study. These microsatellites cover gene loci the encoded protein of which take part in the regulation of apoptosis and (innate) immune processes. Respective loci contribute to the activation/suppression of apoptosis, are involved in signal transduction and cell cycle regulators or they belong to the tumor necrosis factor superfamily, caspase related genes or the BCL2 family. Furthermore, several cytokines as well as chemokines were included. The approach is based on three steps: analyzing pooled DNAs of patients and controls, verification of significantly differing microsatellite markers by genotyping individual DNA samples and, finally, additional reinvestigation of the respective gene in the region covered by the associated microsatellite by analysing single-nucleotide polymorphisms (SNPs). Using this step-wise process we were unable to demonstrate evidence for genetic predisposition of the chosen apoptosis- and immunity-related genes with respect to susceptibility for CD.
Wagenleiter
Sonja E N
SE
Department of Human Genetics, Ruhr-University, Bochum, Germany. sunnie1@gmx.de
Jagiello
Peter
P
Akkad
Denis A
DA
Arning
Larissa
L
Griga
Thomas
T
Klein
Wolfram
W
Epplen
Jörg T
JT
D000483:Alleles; D017209:Apoptosis / Q000235:genetics*; D053301:B-Cell Maturation Antigen / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D053301:B-Cell Maturation Antigen; D005819:Genetic Markers; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C086966:TNFRSF17 protein, human; D015534:Trans-Activators