title: Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients.
abstract: We examined the influence of the cytochrome P450 3A5 (CYP3A5) genes in both donors and recipients on the concentration-dosage ratio (C/D) of tacrolimus in Chinese liver transplant patients. Fifty-one adult liver transplant patients who received tacrolimus were included in this study. The CYP3A5 polymorphism in donors and recipients was determined at the time of transplantation, and tacrolimus-based immunosuppressive therapy was started based on each patient's genetic constitution. The relationship between the C/D of tacrolimus for 3 months after surgery and the CYP3A5 genotype was analyzed. A stepwise regression model was used to analyze the relationship between C/D of tacrolimus and genotype, time course, age, and liver weight in liver transplant patients. Three months after liver transplantation, C/D was both affected by the CYP3A5 genotype of both the donors and the recipients. The C/D of tacrolimus in patients with the CYP3A5*1 allele or carrying CYP3A5*1 allele in the liver was lower than that in CYP3A5*3/*3 patients with the CYP3A5*3/*3 genotype in the liver (P < 0.01). The CYP3A5*1 genotype in donors as well as in patients both contributes to interindividual variation in the C/D of tacrolimus in adult liver transplantation.
authors.affiliation: Department of Surgery and Liver Transplantation Center, Capital Medical University Affiliated to Youan Hospital, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Liberation Army Secondary Artillery Hospital, Beijing, China.
authors.forename: L H
authors.initials: LH
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Liberation Army Secondary Artillery Hospital, Beijing, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Capital Medical University affiliated to Youan Hospital, Beijing, China.
authors.forename: M X
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, General Hospital of PLA, Beijing, China.
authors.forename: S C
authors.initials: SC
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016559:Tacrolimus / Q000008:administration & dosage*; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus