Foote Clary J, Greer Wenda, Kiberd Bryce, Fraser Albert, Lawen Joseph, Nashan Bjorn, Belitsky Philip
Department of Pathology, Queen Elizabeth II Health Sciences Centre/ Dalhousie University, Halifax, NS, Canada.
Transplantation. 2007 May 27;83(10):1380-4. doi: 10.1097/01.tp.0000264197.88129.2e.
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.
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).
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.
MDR1 polymorphisms are associated with differences in CsA exposure only in the first posttransplant week.
多药耐药（MDR1）基因中的几个单核苷酸多态性（SNP）可能在肾移植患者中环孢素A（CsA）吸收的个体间差异中起作用。
对69例接受基因分型检测MDR1 SNP的初发肾移植患者，于移植后第3天进行CsA吸收分析，通过剂量和体重校正的4小时时间 - 浓度曲线下面积AUC(0 - 4)/mg剂量CsA/kg来测定。在移植后1个月进行随访药物基因组学分析，利用剂量和体重校正的给药后2小时CsA浓度（C2）。
术后第3天，(C/C)3435个体的AUC(0 - 4)/mg剂量CsA/kg显著高于(C/T)3435和(T/T)3435患者的分组人群（P = 0.024）。G2677T变异与CsA吸收无显著相关性（P = 0.084）。C3435 - G2677单倍型数量是CsA暴露的最佳预测指标。移植后1个月，未发现MDR1 SNP与CsA暴露之间存在相关性。C3435T和G2677T野生型变异的频率分别为61%和77.6%。发现G2677T和C3435T位点的SNP处于连锁不平衡状态。
MDR1多态性仅在移植后的第一周与CsA暴露差异相关。
