Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in de novo renal transplant patients.
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Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in de novo renal transplant patients. / Foote, Clary J; Greer, Wenda; Kiberd, Bryce; Fraser, Albert; Lawen, Joseph; Nashan, Björn; Belitsky, Philip.
in: TRANSPLANTATION, Jahrgang 83, Nr. 10, 10, 2007, S. 1380-1384.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in de novo renal transplant patients.
AU - Foote, Clary J
AU - Greer, Wenda
AU - Kiberd, Bryce
AU - Fraser, Albert
AU - Lawen, Joseph
AU - Nashan, Björn
AU - Belitsky, Philip
PY - 2007
Y1 - 2007
N2 - BACKGROUND: Several single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene may play a role in the interindividual variation of cyclosporine A (CsA) absorption in renal transplant patients. METHODS: An analysis of CsA absorption measured by the dose- and weight-adjusted 4 hr area under the time-concentration curve, AUC(0-4)/mg doseCsA/kg, was conducted on day 3 after transplantation, in 69 de novo renal transplant patients who were genotyped for MDR1 SNPs. Follow-up pharmacogenomic analysis at 1 month posttransplant was performed utilizing dose- and weight-adjusted 2-hour postdose CsA concentration (C2). RESULTS: AUC(0-4)/mg doseCsA/kg was significantly higher (P=0.024) in (C/C)3435 individuals than in a grouped population of (C/T)3435 and (T/T)3435 patients on postoperative day 3. G2677T variants were not significantly correlated with CsA absorption (P=0.084). The number of C3435-G2677 haplotypes was the best predictor of CsA exposure. At 1 month posttransplant, no correlation was seen between MDR1 SNPs and CsA exposure. The frequency of wild-type variants for C3435T and G2677T were 61% and 77.6%, respectively. SNPs at G2677T and C3435T loci were found to be in linkage disequilibrium. CONCLUSIONS: MDR1 polymorphisms are associated with differences in CsA exposure only in the first posttransplant week.
AB - BACKGROUND: Several single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene may play a role in the interindividual variation of cyclosporine A (CsA) absorption in renal transplant patients. METHODS: An analysis of CsA absorption measured by the dose- and weight-adjusted 4 hr area under the time-concentration curve, AUC(0-4)/mg doseCsA/kg, was conducted on day 3 after transplantation, in 69 de novo renal transplant patients who were genotyped for MDR1 SNPs. Follow-up pharmacogenomic analysis at 1 month posttransplant was performed utilizing dose- and weight-adjusted 2-hour postdose CsA concentration (C2). RESULTS: AUC(0-4)/mg doseCsA/kg was significantly higher (P=0.024) in (C/C)3435 individuals than in a grouped population of (C/T)3435 and (T/T)3435 patients on postoperative day 3. G2677T variants were not significantly correlated with CsA absorption (P=0.084). The number of C3435-G2677 haplotypes was the best predictor of CsA exposure. At 1 month posttransplant, no correlation was seen between MDR1 SNPs and CsA exposure. The frequency of wild-type variants for C3435T and G2677T were 61% and 77.6%, respectively. SNPs at G2677T and C3435T loci were found to be in linkage disequilibrium. CONCLUSIONS: MDR1 polymorphisms are associated with differences in CsA exposure only in the first posttransplant week.
M3 - SCORING: Zeitschriftenaufsatz
VL - 83
SP - 1380
EP - 1384
JO - TRANSPLANTATION
JF - TRANSPLANTATION
SN - 0041-1337
IS - 10
M1 - 10
ER -
