BACKGROUND: P-glycoprotein is a transmembrane efflux pump that extrudes a wide variety of drugs, thereby reducing their intracellular access. In humans, P-glycoprotein is encoded by the MDR1 gene. Recently, several single nucleotide polymorphisms in the MDR1 gene were identified. Moreover, it was postulated that, in addition to the full-length P-glycoprotein, a 'mini' P-glycoprotein was also present in lymphocytes. MATERIALS AND METHODS: We investigated the effect of the genetic polymorphisms G2677T and C3435T in the MDR1 gene on MDR1 mRNA expression in FACS-sorted peripheral blood CD4+, CD8+, CD19+, and CD56+ cells. MDR1 mRNA expression was determined in 45 healthy individuals using a real-time quantitative RT-PCR. RESULTS: We detected the highest expression of MDR1 mRNA in CD56+ cells, followed by CD8+ > CD4+ > CD19+ cells. However, genetic polymorphisms of the MDR1 gene failed to affect (P > 0.05) MDR1 mRNA levels in the peripheral blood lymphocytes. Furthermore, the transcript levels for the MDR1 N-terminal half were almost two-fold lower than that of the MDR1 C-terminal half in all cell populations investigated (P < 0.0001). CONCLUSIONS: An almost two-fold difference in MDR1 C- and N-terminal half expressions supports the presence of mini-P-glycoprotein, an alternatively spliced form of the full-length molecule, in peripheral blood lymphocytes.
BACKGROUND:P-glycoprotein is a transmembrane efflux pump that extrudes a wide variety of drugs, thereby reducing their intracellular access. In humans, P-glycoprotein is encoded by the MDR1 gene. Recently, several single nucleotide polymorphisms in the MDR1 gene were identified. Moreover, it was postulated that, in addition to the full-length P-glycoprotein, a 'mini' P-glycoprotein was also present in lymphocytes. MATERIALS AND METHODS: We investigated the effect of the genetic polymorphisms G2677T and C3435T in the MDR1 gene on MDR1 mRNA expression in FACS-sorted peripheral blood CD4+, CD8+, CD19+, and CD56+ cells. MDR1 mRNA expression was determined in 45 healthy individuals using a real-time quantitative RT-PCR. RESULTS: We detected the highest expression of MDR1 mRNA in CD56+ cells, followed by CD8+ > CD4+ > CD19+ cells. However, genetic polymorphisms of the MDR1 gene failed to affect (P > 0.05) MDR1 mRNA levels in the peripheral blood lymphocytes. Furthermore, the transcript levels for the MDR1 N-terminal half were almost two-fold lower than that of the MDR1 C-terminal half in all cell populations investigated (P < 0.0001). CONCLUSIONS: An almost two-fold difference in MDR1 C- and N-terminal half expressions supports the presence of mini-P-glycoprotein, an alternatively spliced form of the full-length molecule, in peripheral blood lymphocytes.
Authors: Nicole Soranzo; Gianpiero L Cavalleri; Michael E Weale; Nicholas W Wood; Chantal Depondt; Richard Marguerie; Sanjay M Sisodiya; David B Goldstein Journal: Genome Res Date: 2004-06-14 Impact factor: 9.043
Authors: Andrew Owen; Chris Goldring; Paul Morgan; David Chadwick; B Kevin Park; Munir Pirmohamed Journal: Br J Clin Pharmacol Date: 2005-03 Impact factor: 4.335