As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD.
Associations of allelic variants of the multidrug resistance gene (ABCB1 or MDR1) and inflammatory bowel disease and their effects on disease behavior: a case-control and meta-analysis study.
ATP-binding cassette transporter ABCG2 (BCRP) and ABCB1 (MDR1) variants are not associated with disease susceptibility, disease phenotype response to medical therapy or need for surgeryin Hungarian patients with inflammatory bowel diseases.
In order to decrease the uncertainty of pooled risk effects and to explore the trend and stability of the risk effects, a meticulous meta-analysis, including cumulative and recursive cumulative meta-analysis, of the GAS related to the MDR1 gene with susceptibility to IBD was conducted.
Interestingly, a negative association was found between MDR1C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20-0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13-0.68).
More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors.
Our observations suggest that the inhibition of P-gp by COX-2-inhibitors could contribute to the improvement of medical response and this finding may have relevance to medical treatment of inflammatory bowel disease patients.
Potential implications of this reduced mechanism of detoxification will be shown for three selected diseases: (1) association of low intestinal P-glycoprotein expression with development of inflammatory bowel disease; (2) implications for disease risk and therapeutic outcome of HIV; and (3) consequences of this mutation for renal P-glycoprotein expression and risk of renal cell carcinoma.
Since multi-drug resistance 1 gene (MDR1) has a potential influence on Dexamethasone (Dex) bioavailability, we designed this study to investigate the correlation between MDR1 genotype and Dex pharmacokinetic after its delivery in patients with inflammatory bowel disease (IBD).
Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear.
Studies investigating MDR1 gene polymorphism and predisposition to IBD have also shown conflicting results, owing to the known difficulties in complex diseases, especially when the supposed genetic contribution is weak.
The aim of this study was to investigate the G2677T/A polymorphism in the MDR1 gene in Turkish patients with inflammatory bowel disease and a healthy control group.
The Ala893 variant has decreased activity compared with the 893Ser variant; therefore, the association with human IBD is consistent with the murine model of mdr1 deficiency.