Objective: To investigate the association of MDR1 and NFKBIA polymorphisms with cyclosporine concentrations in Chinese renal transplant recipients.
Method: A total of 88 renal transplant recipients receiving cyclosporine were genotyped by polymerase chain reaction–restriction fragment length polymorphism for MDR1 G2677T/A, C3435T, and NFKBIA G2758A. Cyclosporine whole blood levels were measured by ﬂuorescence polarization immunoassay.Trough concentration (C0) of cyclosporine during days 6-18 after transplantation was determined.
Results: Dose-adjusted C0 of cyclosporine in MDR1 2677TT carriers was significant higher than those in GG plus GT carriers (90.38±24.46 vs. 66.89±25.66 ng/mL per mg/kg, P<0.001). MDR1 3435TT carriers had significant higher dose-adjusted C0 of cyclosporine than those in CC plus CT carriers (91.96±24.01 vs. 68.95±26.82 ng/mL per mg/kg, P=0.002). When combined the effects of MDR1 G2677T/A and C3435T, the carriers of haplotype T-T had an obviously higher dose-adjusted C0 of cyclosporine than carriers of other haplotypes (97.23±21.78 vs. 68.38±26.36 ng/mL per mg/kg, P<0.0001). In addition, dose-adjusted C0 of cyclosporine in NFKBIA 2758AA carriers were significant higher than those in GA plus GG carriers (81.93±27.37 vs. 59.77±22.97 ng/mL per mg/kg, P<0.0001). In this analysis, MDR1 G2677T/A and NFKBIA G2758A contributed most to the inter-individual variability in cyclosporine trough concentration, accounting for 24.6% and 14.6%, respectively.
Conclusion: These results indicated that MDR1 2677TT, 3435TT and NFKBIA 2758AA genotype were closely correlated with cyclosporine trough concentrations. It suggested that these SNPs may play a key role in optimal dosing regimen of cyclosporine.
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