[Relationship between MDR1 gene polymorphism and blood concentration of tacrolimus in renal transplant patients].
OBJECTIVE
To investigate the relationship between MDR1 exon 21 and exon 26 polymorphism and whole blood concentration of tacrolimus (FK506) in renal transplant patients.


METHODS
Blood samples were collected from 86 renal transplant patients who received FK506 peri-operationally. PCR-RELP was used to determine the MDR1 genotype. The patients were divided into 3 subgroups for every position: GG, GT, and TT in exon 21; and CC, CT, and TT in exon 26. Three, six, and twelve months after the transplantation ELISA was used to measure the whole blood concentration of FK506. The FK506 concentrations standardized by dosage and body weight (FK506 concentration per dose/kg) were compared among the 3 subgroups within the MDR1 exon 21 and exon 26 groups.


RESULTS
Of the 86 patients 26 (30.2%), 35 (40.7%), and 25 (29.1%) were carriers of GG, GT, and TT in exon 21, and 26 (30.2%), 35 (40.7%), and 23 (26.8%) were carriers of CC, CT, and TT in exon 26. MDR1 exon 26 C3435T was in significant linkage disequilibrium with MDR1 exon 21 G2677T. Three, six, and twelve months after the transplantation a significant correlation between the whole blood FK506 concentration per dose/day and MDR1 exon 21 and exon 26 genotypes. For exon 21 there were significant differences among the 3 subgroups (all P < 0.01). The ratio for the patients with GG was remarkably lower than that of those with GT and TT, and the ratio with GT was also lower than the patients with TT (P < 0.05). For exon 26, there was also a significant difference among the 3 subgroups (all P < 0.01). The ratio for the patients with CC was remarkably lower than those of the patients with CT and TT, and the ratio of CT was also lower than that of TT (P < 0.05).


CONCLUSIONS
The MDR1 gene polymorphism is correlated with the whole blood concentration of FK506. To obtain the similar blood concentration of FK506, the patients with GG and CC should take the drug at a higher dose than those with Ct and TT.
Wang
Wei
W
Department of Urology, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020, China. zico73@medmail.com.cn
Zhang
Xiao-dong
XD
Ma
Lin-lin
LL
Lü
Yue-ping
YP
Hu
Xiao-peng
XP
Zhang
Peng
P
Wang
Yong
Y
Guan
De-lin
DL
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016559:Tacrolimus