Abstract:
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.
journal_name
Transplantationjournal_title
Transplantationauthors
Foote CJ,Greer W,Kiberd B,Fraser A,Lawen J,Nashan B,Belitsky Pdoi
10.1097/01.tp.0000264197.88129.2esubject
Has Abstractpub_date
2007-05-27 00:00:00pages
1380-4issue
10eissn
0041-1337issn
1534-6080pii
00007890-200705270-00015journal_volume
83pub_type
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