PURPOSE: This study investigated whether haplotypes in the multidrug resistance 1 (MDR1) gene had effects on mRNA expression levels of MDR1 and cytochrome P450 (CYP) 3A4, and on the pharmacokinetics of tacrolimus in living-donor liver transplant (LDLT) patients, considering the gender difference. METHODS: Haplotype analysis of MDR1 with G2677T/A and C3435T was performed in 63 de novo Japanese LDLT patients (17 to 55 years; 44.4% women). The expression levels of MDR1 and CYP3A4 mRNAs in jejunal biopsy specimens were quantified by real-time PCR. RESULTS: Intestinal CYP3A4 mRNA expression levels (amol/microg total RNA) showed significantly higher values in women carrying the 2677TT-3435TT haplotype (median, 10.7; range, 5.92-15.2) than those with 2677GG-3435CC (3.03; range 1.38-4.68) and 2677GT-3435CT (median, 4.31; range, 0.07-9.42) (P = 0.022), but not in men (P = 0.81). However, MDR1 haplotype did not influence mRNA expression levels of MDR1 nor the concentration/dose ratio [(ng/mL)/(mg/day)] of oral tacrolimus for the postoperative 7 days, irrespective of gender. CONCLUSION: MDR1 haplotype may have a minor association with the tacrolimus pharmacokinetics after LDLT, but could be a good predictor of the inter-individual variation of intestinal expression of CYP3A4 in women.
PURPOSE: This study investigated whether haplotypes in the multidrug resistance 1 (MDR1) gene had effects on mRNA expression levels of MDR1 and cytochrome P450 (CYP) 3A4, and on the pharmacokinetics of tacrolimus in living-donor liver transplant (LDLT) patients, considering the gender difference. METHODS: Haplotype analysis of MDR1 with G2677T/A and C3435T was performed in 63 de novo Japanese LDLT patients (17 to 55 years; 44.4% women). The expression levels of MDR1 and CYP3A4 mRNAs in jejunal biopsy specimens were quantified by real-time PCR. RESULTS: Intestinal CYP3A4 mRNA expression levels (amol/microg total RNA) showed significantly higher values in women carrying the 2677TT-3435TT haplotype (median, 10.7; range, 5.92-15.2) than those with 2677GG-3435CC (3.03; range 1.38-4.68) and 2677GT-3435CT (median, 4.31; range, 0.07-9.42) (P = 0.022), but not in men (P = 0.81). However, MDR1 haplotype did not influence mRNA expression levels of MDR1 nor the concentration/dose ratio [(ng/mL)/(mg/day)] of oral tacrolimus for the postoperative 7 days, irrespective of gender. CONCLUSION:MDR1 haplotype may have a minor association with the tacrolimus pharmacokinetics after LDLT, but could be a good predictor of the inter-individual variation of intestinal expression of CYP3A4 in women.
Authors: Chava Kimchi-Sarfaty; Andrew H Marple; Shiri Shinar; Avraham M Kimchi; David Scavo; M Isabella Roma; In-Wha Kim; Adam Jones; Mili Arora; John Gribar; David Gurwitz; Michael M Gottesman Journal: Pharmacogenomics Date: 2007-01 Impact factor: 2.533
Authors: Renzo Wolbold; Kathrin Klein; Oliver Burk; Andreas K Nüssler; Peter Neuhaus; Michel Eichelbaum; Matthias Schwab; Ulrich M Zanger Journal: Hepatology Date: 2003-10 Impact factor: 17.425
Authors: Deanna L Kroetz; Christiane Pauli-Magnus; Laura M Hodges; Conrad C Huang; Michiko Kawamoto; Susan J Johns; Doug Stryke; Thomas E Ferrin; Joseph DeYoung; Travis Taylor; Elaine J Carlson; Ira Herskowitz; Kathleen M Giacomini; Andrew G Clark Journal: Pharmacogenetics Date: 2003-08
Authors: M Yasuhara; T Hashida; M Toraguchi; Y Hashimoto; M Kimura; K Inui; R Hori; Y Inomata; K Tanaka; Y Yamaoka Journal: Transplant Proc Date: 1995-02 Impact factor: 1.066
Authors: Abdullah M Al-Mohizea; Khalid M Alkharfy; Khawla M Bagulb; Amal M Alghamdi; Fahad I Al-Jenoobi; Saleh Al-Muhsen; Rabih Halwani; Mohammad Khalid Parvez; M Khalid Parvez; Mohammed S Al-Dosari Journal: Mol Biol Rep Date: 2012-10-07 Impact factor: 2.316
Authors: Wai-Johnn Sam; Christine E Chamberlain; Su-Jun Lee; Joyce A Goldstein; Douglas A Hale; Roslyn B Mannon; Allan D Kirk; Yuen Yi Hon Journal: Transplantation Date: 2011-12-27 Impact factor: 4.939
Authors: Saskia N de Wildt; Ron H N van Schaik; Offie P Soldin; Steve J Soldin; Parvaneh Yazdani Brojeni; Ilse P van der Heiden; Chris Parshuram; Irena Nulman; Gideon Koren Journal: Eur J Clin Pharmacol Date: 2011-06-23 Impact factor: 2.953