Our data highlight important and novel findings pertaining to CD-associated changes to the intestinal expression of CYP3A4 and P-gp that are of relevance to better predict substrate drug dosing for patients with CD.
In contrast, a recent study reported that multidrug resistance protein 1 (MDR1) regulated effector T-cell function in the ileum from bile acid-driven oxidative stress and MDR1 loss of function in a subset of patients with Crohn's disease.
Our aim was to elucidate the activity of CYP3A4 and P-gp in subjects with Crohn's disease (CD) and to evaluate their influence on budesonide pharmacokinetics.
Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1<sup>-/-</sup> hosts.
Our results demonstrated that the sustained chronic inflammation could induce the intrinsic resistance presented as P-gp over-expression in PBMC in Crohn's disease through STAT3/Nf-κb pathway and this resistance might be reversed by combinational usage of P-gp inhibitors.
Contrary to the first 2 categories, genes involved in xenobiotic activity, such as ABCB1, had lower expression in the pouchitis and Crohn's disease-like groups compared with the no pouchitis and familial adenomatous polyposis groups.
Besides, stratified analysis by clinical type also indicated that no significant association between MDR1C3435T and the risk of Crohn's disease and ulcerative colitis was observed.
The expression level of the ABCB1/MDR1 gene which encodes P-glycoprotein seems to be of great prognostic relevance while evaluating patients' susceptibility to UC or CD.
Three hundred eighty-eight German IBD patients [244 with Crohn's disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T.
In our pediatric cohort, the promoter -308A polymorphism of TNF-alpha but not the MDR1 gene is significantly involved in the predisposition to both CD and UC.
This 'candidate gene' approach provides compelling evidence to support the contribution of the ABCB1/MDR1 gene in determining risk to UC but not to CD and provides new insights into the localization of the critical susceptibility determinants within the gene.
This was a case-control analysis of MDR1C3435T and G2677T SNPs in a large well-characterized Scottish white cohort (335 with ulcerative colitis [UC], 268 with Crohn's disease [CD], and 370 healthy controls).
Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P-glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease.
Relative amounts of MDR1 mRNA expressed in peripheral blood mononuclear cells (PBMCs) were measured using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique in 25 UC patients having no history of GC administration, 25 UC patients having experienced GC therapy, 19 patients with Crohn's disease (CD) with no history of GC therapy, and 27 healthy subjects.