The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation.

The impact of single nucleotide polymorphisms of two loci (C3435T and G2677T/A) of the multidrug resistance-1 gene (MDR1) was investigated in 82 patients undergoing allogeneic stem cell transplantation (SCT). The GG genotype on G2677T/A loci was associated with higher non-relapse mortality than was the non-GG genotype (67% vs. 32%, p=0.0073), but not the C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival was significantly correlated with the G2677T/A genotype (p=0.0048). Multivariate analysis also showed that the GG genotype at G2677T/A had an unfavorable prognosis in terms of overall survival (p=0.003) and non-relapse mortality (p=0.031). In conclusion, the G2677T/A genotype seems to be associated with transplantation outcomes, especially non-relapse mortality.

[1]  J. Park,et al.  Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia. , 2005, International journal of cancer.

[2]  W. Weimar,et al.  Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR‐1, CYP3A4, and CYP3A5 genes , 2004, Clinical pharmacology and therapeutics.

[3]  E. Thervet,et al.  Pharmacogenetics in solid organ transplantation: present knowledge and future perspectives. , 2004, Transplantation.

[4]  D. Tregouet,et al.  CYP3A5 and MDR1 Genetic Polymorphisms and Cyclosporine Pharmacokinetics After Renal Transplantation , 2004, Clinical pharmacology and therapeutics.

[5]  S. Sohn,et al.  Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation , 2004, British journal of haematology.

[6]  J. Squifflet,et al.  The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. , 2004, Pharmacogenetics.

[7]  Thierry Buclin,et al.  Polymorphisms in Human MDR1 (P‐glycoprotein): Recent Advances and Clinical Relevance , 2004, Clinical pharmacology and therapeutics.

[8]  W. Weimar,et al.  Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR‐1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus , 2003, Clinical pharmacology and therapeutics.

[9]  Y. Cheung,et al.  Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. , 2003, Pharmacogenetics.

[10]  M. Fromm.  The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. , 2002, Advanced drug delivery reviews.

[11]  R. Kim,et al.  MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. , 2002, Cancer research.

[12]  E. Schuetz,et al.  The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients. , 2002, Human immunology.

[13]  Keizo Sugimachi,et al.  Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene , 2002, Transplantation.

[14]  S. Uemoto,et al.  C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation. , 2002, Pharmacogenetics.

[15]  R. Kim,et al.  Identification of functionally variant MDR1 alleles among European Americans and African Americans , 2001, Clinical pharmacology and therapeutics.

[16]  M. Fromm,et al.  The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. , 2001, Pharmacogenetics.

[17]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[18]  U. Brinkmann,et al.  Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[20]  R. Johnson,et al.  Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. , 1979, Cancer research.