[Association of CYP3A5 and MDR1 genetic polymorphisms with the blood concentration of tacrolimus in Chinese liver and renal transplant recipients].
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.
Institute of Drug Clinical Trial, West China Hospital, Sichuan University, Chengdu 610041, China.
Jia-Yu
JY
Sun
Xian-Gang
XG
Wang
Yuan-Gao
YG
Zou
Yan-ping
YP
Wang
De-Rong
DR
Liang
Mao-Zhi
MZ
Liang
Jia
J
Miao
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus