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Volume 44 Issue 4
Jul.  2013
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SUN Jia-yu, WANG Xian-gang, ZOU Yuan-gao, et al. Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients[J]. Journal of Sichuan University (Medical Sciences), 2013, 44(4): 573-577.
Citation: SUN Jia-yu, WANG Xian-gang, ZOU Yuan-gao, et al. Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients[J]. Journal of Sichuan University (Medical Sciences), 2013, 44(4): 573-577.
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Association of CYP3A5 and MDR1 Genetic Polymorphisms with the Blood Concentration of Tacrolimus in Chinese Liver and Renal Transplant Recipients

  • 1. Institute of Drug Clinical Trial, West China Hospital, Sichuan University, Chengdu 610041, China;

  • 2. Department of Respiratoty Medicine, the First People's Hospital of Neijiang, Neijiang 641000, China;

  • 3. Immunopharmacology laboratory of Medical Experiments Division, West China Hospital, Sichuan University, Chengdu 610041, China;

  • 4. Tumor Molecular Diagnostic Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China

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  • Received Date: December 20, 2012
  • Revised Date: April 28, 2013
  • Published Date: July 19, 2013
    Abstract
  • 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.
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    • References (15)
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