Objective: To investigate the association of CYP3A5 and MDR1 genetic polymorphisms with the concentration/ dose (C/D) ratio of tacrolimus for the feasibility of individualized medication.
Methods: The concentration of tacrolimus was detected by enzyme-multiplied immunoassay technique, and was adjusted by weight and dosage to C/D ratios. The single nucleotide polymorphisms of CYP3A5 A6986G and MDR1 C3435T, G2677T/ A, T1236C were determined by TaqMan RT-PCR. The differences of C/D ratio were compared among all of the genotype groups.
Results: There were 5 cases with CYP3A5 *1/*1, 22 cases with CYP3A5 *1/*3, and 33 cases with CYP3A5 *3/*3. The C/D ratios of the patients with at least one CYP3A5 *1 allele (130.40 +/- 53.94) was significantly lower than those with CYP3A5 *3/*3 (198.12 +/- 90.80) (P < 0.01). For MDR1, there were 22, 23 and 15 recipients carried C/C, C/T and T/T respectively in C3435T, and 8, 32 and 20 recipients carried T/T, T/ C and C/C respectively in T1236C. The carriers with G/G, G/T, G/A, T/A, T/T were 9, 24, 5, 8 and 14 respectively in G2677T/A. No significant difference was found in the C/D ratios of tacrolimus among different MDR1 genotypes.
Conclusions: Determination of CYP3A5 genotype could help individualize tacrolimus dose regimen prospectively. The patients with CYP3A5 *3 *3 require less dose of tacrolimus to reach the same concentrations comparing with the patients with at least one CYP3A5 * 1 allele.