[Relationship between MDR1 gene polymorphism and blood concentration of tacrolimus in renal transplant patients].

Abstract

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.

• Authors: Wei Wang, Xiao-dong Zhang, Lin-lin Ma, Yue-ping Lü, Xiao-peng Hu, Peng Zhang, Yong Wang, De-lin Guan
• Journal: Zhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 85 Issue 46 Pg. 3277-81 (Dec 07 2005) ISSN: 0376-2491 [Print] China
• PMID: 16409819 (Publication Type: Journal Article)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Immunosuppressive Agents
• Tacrolimus

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adult
• Enzyme-Linked Immunosorbent Assay
• Exons
• Female
• Gene Frequency
• Genotype
• Humans
• Immunosuppressive Agents (pharmacokinetics, therapeutic use)
• Kidney Transplantation
• Male
• Middle Aged
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Tacrolimus (blood, pharmacokinetics, therapeutic use)