MDR1 gene expression in lymphocytes of patients with renal transplants.
The MDR1 gene, a multidrug resistance gene, codes for P-glycoprotein which pumps hydrophobic drugs out of the cells. Since cyclosporins also bind to P-glycoprotein and might be pumped by this transmembrane protein, we determined the expression of the MDR1 gene in the lymphocytes of 32 patients with renal transplants. MDR1 RNA expression of lymphocytes was measured by slot blot analysis and compared to the expression of drug-sensitive KB-3-1 cells and multidrug-resistant KB-8-5 cells. MDR1 RNA expression was detected in the lymphocytes of 9 (28%) patients, whereas no expression was seen in the remaining 23 patients. No association between MDR1 RNA expression and transplant function or hematological parameters was observed. However, none of the 6 patients who had transplants for more than 40 months expressed the MDR1 gene in their lymphocytes. In conclusion, expression of the MDR1 gene does occur in lymphocytes of patients with renal transplants and might reduce the immunosuppressive efficacy of cyclosporins through enhanced efflux of cyclosporins.
Götzl
M
M
Clinic for Internal Medicine I and III, University of Vienna Medical School, Austria.
Wallner
J
J
Gsur
A
A
Zöchbauer
S
S
Kovarik
J
J
Balcke
P
P
Pirker
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000473:pathology; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D012313:RNA / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012313:RNA; D016572:Cyclosporine