Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients
Abstract
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.
Keywords: Tacrolimus, Cytochrome P450 3A5, Multidrug resistance 1, P-glycoprotein, Single nucleotide polymorphisms
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