Donors FMO3 polymorphisms affect tacrolimus elimination in Chinese liver transplant patients

被引：11
作者：
Ren, Lei [1 ]
Teng, Mujian [1 ]
Zhang, Tao [2 ]
Zhang, Xiaoqing [3 ]
Sun, Bo [4 ]
Qin, Shengying [5 ]
Zhong, Lin [2 ]
Peng, Zhihai [2 ]
Fan, Junwei [2 ]
机构：
[1] Shandong Univ, Shandong Qianfoshan Hosp, Dept Hepatobiliary Pancreat Surg, Jinan 250014, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Hepatobiliary Pancreat Surg, Shanghai 200080, Peoples R China
[3] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Pharm, Shanghai 200433, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Dept Pharm, Shanghai Peoples Hosp 1, Shanghai 200080, Peoples R China
[5] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai 200030, Peoples R China
来源：
PHARMACOGENOMICS | 2017年 / 18卷 / 03期
基金：
中国国家自然科学基金;
关键词：
CYP-450; 3A5; FMO3; pharmacogenomics; tacrolimus; FLAVIN-CONTAINING MONOOXYGENASES; FAMILIAL ADENOMATOUS POLYPOSIS; DRUG-METABOLIZING-ENZYMES; GENETIC POLYMORPHISMS; PHARMACOKINETICS; CYP3A5; GENOTYPE; FLAVIN-MONOOXYGENASE-3; IDENTIFICATION; PERSPECTIVES;
D O I：
10.2217/pgs-2016-0098
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Aim: Flavin-containing monooxygenase (FMO) variants were potentially involved in tacrolimus metabolism in kidney transplantion. The influences of FMO3 genotypes on tacrolimus elimination in Chinese liver transplant patients remained unclear. Patients & methods: FMO3 SNPs and CYP3A5 rs776746 were analyzed in 110 Chinese patients. Results: Donor FMO3 rs1800822 allele T and rs909530 allele T were associated with fast tacrolimus elimination. Combination of polymorphisms of donor FMO3 rs1800822 and rs909530 genotype impacted on tacrolimus elimination (p = 0.0221). The number of donor rs1800822 allele T and rs909530 allele T was confirmed to be an independent predictor of the tacrolimus concentration-to-dose ratios for weeks 2, 3 and 4 in the multivariate analysis. Conclusion: Donor's FMO3 polymorphisms might affect tacrolimus elimination.
引用
收藏
页码：265 / 275
页数：11
相关论文
共 35 条
  • [1] Pharmacogenomics Variation in Drug Metabolizing Enzymes and Transporters in Relation to Docetaxel Toxicity in Lebanese Breast Cancer Patients: Paving the Way for OMICs in Low and Middle Income Countries
    Awada, Zainab
    Haider, Syed
    Tfayli, Arafat
    Bazarbachi, Ali
    El-Saghir, Nagi S.
    Salem, Ziad
    Shamseddine, Ali
    Taher, Ali
    Zgheib, Nathalie Khoueiry
    [J]. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, 2013, 17 (07) : 353 - 367
  • [2] Calcineurin inhibitors in liver transplantation still champions or threatened by serious competitors?
    Beckebaum, Susanne
    Cicinnati, Vito R.
    Radtke, Arnold
    Kabar, Iyad
    [J]. LIVER INTERNATIONAL, 2013, 33 (05) : 656 - 665
  • [3] Influence of SLCO1B3 Genetic Variations on Tacrolimus Pharmacokinetics in Renal Transplant Recipients
    Bolvin, Andree-Anne
    Cardinal, Heloise
    Barama, Azemi
    Naud, Judith
    Pichette, Vincent
    Hebert, Marie-Josee
    Roger, Michel
    [J]. DRUG METABOLISM AND PHARMACOKINETICS, 2013, 28 (03) : 274 - 277
  • [4] Carbamazepine-Induced Toxic Effects and HLA-B*1502 Screening in Taiwan
    Chen, Pei
    Lin, Juei-Jueng
    Lu, Chin-Song
    Ong, Cheung-Ter
    Hsieh, Peiyuan F.
    Yang, Chih-Chao
    Tai, Chih-Ta
    Wu, Shey-Lin
    Lu, Cheng-Hsien
    Hsu, Yung-Chu
    Yu, Hsiang-Yu
    Ro, Long-Sun
    Lu, Chung-Ta
    Chu, Chun-Che
    Tsai, Jing-Jane
    Su, Yu-Hsiang
    Lan, Sheng-Hsing
    Sung, Sheng-Feng
    Lin, Shu-Yi
    Chuang, Hui-Ping
    Huang, Li-Chen
    Chen, Ying-Ju
    Tsai, Pei-Joung
    Liao, Hung-Ting
    Lin, Yu-Hsuan
    Chen, Chien-Hsiun
    Chung, Wen-Hung
    Hung, Shuen-Iu
    Wu, Jer-Yuarn
    Chang, Chi-Feng
    Chen, Luke
    Chen, Yuan-Tsong
    Shen, Chen-Yang
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (12) : 1126 - 1133
  • [5] de Jonge Hylke, 2008, Transplant Rev (Orlando), V22, P6, DOI 10.1016/j.trre.2007.09.002
  • [6] A "silent" nucleotide substitution in exon 4 is responsible for the "alternative expression" of HLA-A*01:01:38L through aberrant splicing
    Dunn, Paul P. J.
    Hammond, Laura
    Coates, Ernest
    Street, Jane
    Griner, Leon
    Darke, Christopher
    [J]. HUMAN IMMUNOLOGY, 2011, 72 (09) : 717 - 722
  • [7] Impact of CYP3A4*22 Allele on Tacrolimus Pharmacokinetics in Early Period After Renal Transplantation: Toward Updated Genotype-Based Dosage Guidelines
    Elens, Laure
    Capron, Arnaud
    van Schaik, Ron H. N.
    De Meyer, Martine
    De Pauw, Luc
    Eddour, Djamila C.
    Latinne, Dominique
    Wallemacq, Pierre
    Mourad, Michel
    Haufroid, Vincent
    [J]. THERAPEUTIC DRUG MONITORING, 2013, 35 (05) : 608 - 616
  • [8] Calcineurin inhibitor minimization protocols in liver transplantation
    Farkas, Stefan A.
    Schnitzbauer, Andreas A.
    Kirchner, Gabi
    Obed, Aiman
    Banas, Bernhard
    Schlitt, Hans J.
    [J]. TRANSPLANT INTERNATIONAL, 2009, 22 (01) : 49 - 60
  • [9] Haplotype frequency distribution and linkage disequilibrium analysis of single nucleotide polymorphisms at the human FMO3 gene locus
    Hao, Da-Cheng
    Sun, Jie
    Furnes, Bjarte
    Schlenk, Daniel
    Hou, Zhen-Fang
    Zhang, Ya-Ping
    Yang, Sheng-Li
    Yang, Ling
    [J]. BIOCHEMICAL GENETICS, 2006, 44 (7-8) : 391 - 407
  • [10] Allele and genotype frequencies of polymorphic FMO3 gene in two genetically distinct populations
    Hao, DaCheng
    Sun, Jie
    Furnes, Bjarte
    Schlenk, Daniel
    Li, MiaoXin
    Yang, ShengLi
    Yang, Ling
    [J]. CELL BIOCHEMISTRY AND FUNCTION, 2007, 25 (04) : 443 - 453
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