title: CYP3A5 and ABCB1 genotype influence tacrolimus and sirolimus pharmacokinetics in renal transplant recipients.
abstract: CYP3A5 and ABCB1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements, but the conclusion in the current reports were inconformity. Sirolimus are also metabolized by CYP3A subfamily and are substrates of the P-gp. The aim was to determine whether these polymorphisms affect tacrolimus (TAC) and sirolimus (SRL) trough concentrations and dose requirements after renal transplantation. 153 renal transplant recipients were enrolled into this study, 112 were treated with TAC-based regimen, Another 43 recipients received SRL-based regimen. The recipients' mean follow-up time was 20 mo (range 15-27 mo). All renal transplant recipients were all in a stable stage. The trough concentration and daily dose of TAC and SRL were gained from each recipient. All recipients were genotyped for CYP3A5 (6986A>G), CYP3A4 intron 6 (CYP3A4*22), CYP3A4*18, ABCB1 exon 26 (3435C>T), exon 12 (1236C>T) and 2677G>T/A SNPs by HRM analysis (high-resolution melting curve analysis). The TAC and SRL concentration/dose ratio (C/D) in recipients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (P < 0.05). However, there was no significant correlation between adjusted TAC and SRL trough concentrations or dose requirements with CYP3A4 and ABCB1 SNPs genetic polymorphisms. In recipients with TAC-based or SRL-based therapy, the CYP3A5 genes (6986A>G) can influence the TAC and SRL pharmacokinetics in renal transplant recipients.
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Yangjuan
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, 610041 The People's Republic of China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
keywords: CYP3A5 and ABCB1; Pharmacokinetics; Polymorphism; Renal transplantation; Sirolimus; Tacrolimus