title: Biological interactions of CYP2C19 genotypes with CYP3A4*18, CYP3A5*3, and MDR1-3435 in living donor liver transplantation recipients.
abstract: BACKGROUND
  Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. The CYP3A4*18, CYP3A5*3, and MDR1-3435 variant alleles are very important, particularly in tacrolimus metabolism in organ transplant rejection.
  
  
  OBJECTIVE
  The aim of this study is o explore possible interactions among different CYP2C19 genotypes, namely, between homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers (HetEM), and poor metabolizers (PM), and the CYP3A4*18, CYP3A5*3, and MDR1-3435 variants in living donors and patients who received a living donor liver transplant (LDLT).
  
  
  METHODS
  This prospective study enrolled 133 living donors and 133 corresponding recipients. On the basis of the HomEM, HetEM, and PM CYP2C19 genotypes, the distributions of CYP3A4*18 (exon 10; T878C), CYP3A5*3 (intron 3; A6986G), and MDR1-3435 (exon 26; C3435T) genotypes were analyzed for single nucleotide polymorphisms among donors and recipients.
  
  
  RESULTS
  Among 102 HomEM genotypes, including 56 donors and 46 recipients, 91.2% of individuals harbored the T/T genotype of CYP3A4*18; 53.9% possessed G/G, and 34.3% had A/G genotypes of CYP3A5*3; and 38.2% had C/C and 50.0% had C/T genotypes at MDR1-3435. Among 130 HetEM genotypes, including 58 donors and 72 recipients, 97.7% of individuals possessed T/T genotype at CYP3A4*18; 50.0% harbored G/G and 41.5% had A/G genotypes at CYP3A5*3; and 40.0% had C/C and 49.2% had C/T genotypes at MDR1-3435. In 34 PMs, including 19 donors and 15 recipients, 88.2% had T/T genotypes at CYP3A4*18; 41.2% had G/G and 58.8% had A/G genotypes at CYP3A5*3; and 47.1% possessed C/C and 47.1% had C/T genotypes at MDR1-3435. On the basis of the CYP2C19 genotypes, no statistically significant distribution of genotypes were observed between donors and recipients for all genotypes of CYP3A4*18, CYP3A5*3, and MDR1-3435 (P >0.05).
  
  
  CONCLUSIONS
  In conclusion, the CYP2C19 genotypes do not affect the expression of CYP3A4*18, CYP3A5*3, or MDR1-3435 variants, which are independently distributed among donors and recipients during LDLT.
authors.affiliation: Liver Transplant Program, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan. c471026@ms6.hinet.net.
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.forename: Tsung-Hui
authors.initials: TH
authors.lastname: Hu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Kuang-Den
authors.initials: KD
authors.lastname: Chen
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Tseng
authors.forename: Ho-Ching
authors.initials: HC
authors.lastname: Chiu
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen