Associations of FMO1 polymorphisms with tacrolimus concentration in renal transplant recipients
10.13699/j.cnki.1001-6821.2024.24.023
- VernacularTitle:FMO1基因多态性与肾移植患者他克莫司浓度的相关性研究
- Author:
Xiao-li ZHONG
1
;
Yi-shu ZHANG
;
Huan-xi ZHANG
;
Chang-xi WANG
;
Min HUANG
;
Jia-li LI
Author Information
1. 中山大学药学院临床药理研究所,广东 广州 510080
- Publication Type:Journal Article
- Keywords:
tacrolimus;
flavin-containing monooxygenase 1;
polymorphism;
renal transplantation
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(24):3635-3639
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the associations of flavin-containing monooxygenase 1(FMO1)polymorphisms with tacrolimus concentration in early post-renal transplant recipients.Methods Post-transplant patients treated with triple immunotherapy(mycophenolic acid+tacrolimus+prednisone)were included.CYP3A5*3 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method and FMO1(rs10912675 and rs7877)genotypes were detected by Agena Bioscience MassARRAY? system.Steady state trough concentrations of tacrolimus on day 6-10 after renal transplantation were collected from clinical data.Correlations between genetic polymorphisms and tacrolimus dose adjusted trough concentration(C0/D)were analyzed by SPSS.Results A total of 176 post-transplant patients were included.The C0/D of tacrolimus in CYP3A5*1/*1 and CYP3A5*1/*3 carriers(CYP3A5 expressers)was significantly lower than that in CYP3A5*3/*3(CYP3A5 nonexpressers)(P＜0.05).A considerably higher C0/D of tacrolimus was found in FMO1 rs10912675 CC carriers than that in CT and TT carriers(P＜0.05).FMO1 rs7877 TT carriers had a higher C0/D of tacrolimus level compared with CT and CC carriers(P＜0.05).After stratification by CYP3A5*3 genotype,a higher C0/D of tacrolimus were observed in FMO1 rs10912675 CC carriers than that in CT and TT carriers in CYP3A5 expressers(P＜0.05).Conclusion The results illustrated that FMO1 rs10912675 polymorphisms were associated with tacrolimus concentrations,suggesting that tacrolimus may be a substrate of FMO1 and genotyping for this SNP may provide a g a new reference for clinical dose prediction of tacrolimus.
