Laboratory Medicine ›› 2015, Vol. 30 ›› Issue (11): 1091-1095.DOI: 10.3969/j.issn.1673-8640.2015.11.008

• Orginal Article • Previous Articles     Next Articles

The influence of CYP3A4, CYP3A5 and CYP2D6 single nucleotide polymorphism on tacrolimus metabolism in renal transplantation patients during stable period

ZHOU Yiwen, ZHOU Yan, WU Jiong, JU Yinghui, GUO Wei   

  1. Department of Clinical Laboratory, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • Received:2015-01-30 Online:2015-11-30 Published:2015-12-03

Abstract: Objective

To investigate the influence of cytochrome P450 CYP3A4, CYP3A5 and CYP2D6 single nucleotide polymorphism on tacrolimus (FK506) metabolism, and to study the feasibility of personalized base treatment of FK506.

Methods

A total of 138 renal transplantation patients during stable period were followed up. All patients received FK506, mycophenolate mofetil and prednisolone treatment. Drug dose per body weight was recorded, the trough concentration of FK506 was calculated, and gene sequencing was used to detect single nucleotide polymorphism of CYP3A4, CYP3A4 and CYP2D6. The drug dose per body weight of FK506 and its relationship with single nucleotide polymorphism were analyzed.

Results

Among the 138 patients genotyped for CYP3A4, 138 patients displayed wild type TT (allele frequency 0.993), heterozygous TC (0.007). There were CYP3A5 wild type AA (0.529), heterozygous AG (0.399) and homozygous GG (0.072 ). CYP2D6 showed 76 case of wild type CC (0.550) and heterozygous CT (0.449). Compared to heterozygous and homozygous alleles, CYP3A5 wild type (AA) and mutant type (AG and GG) expressed higher FK506 dose (P<0.001). CYP2D6 wild type (CC) and mutant type (CT) had no statistical significance with FK506 dose(P>0.05) .

Conclusions

The CYP3A4 genotype polymorphism is mainly wild type, and the significance for FK506 metabolism is minimal. CYP3A5 has a major role in FK506 metabolism, and the patients with wild type need high dose of FK506. The CYP2D6 polymorphism has no correlation with FK506 metabolism.

Key words: Cytochrome P450, Renal transplantation, Tacrolimus, Therapeutic drug monitoring

CLC Number: