Interactive Effects of Cyp3A4, Cyp3A5, Mdr1 and Nr1I2 Polymorphisms on Tracrolimus Trough Concentrations in Early Postrenal Transplant Recipients

• DOI: 10.2217/pgs.15.78
• Publication Date: 2015-07-31T11:17:40Z
• Authors: Jia-li Li; Shu Liu; Qian Fu; Yu Zhang; Xue-ding Wang; Xiao-man Liu; Long-shan Liu; Chang-xi Wang; Min Huang
• Keywords: Adult; Male; Receptors, Steroid; ATP Binding Cassette Transporter, Subfamily B; Adolescent; Genotype; Pregnane X Receptor; Middle Aged; Kidney Transplantation; Polymorphism, Single Nucleotide; Tacrolimus; Transplant Recipients; 3. Good health; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Cytochrome P-450 CYP3A; Humans; Female; Immunosuppressive Agents; Aged

To evaluate the influences of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tacrolimus concentration in early postrenal transplant recipients.A total of 159 patients were included, dose-adjusted tacrolimus trough concentration on day 7 after transplantation (C0D7/D) was calculated and 10 SNPs in four genes were genotyped.CYP3A5*3 explained 32.8% of variability of tacrolimus C0D7/D. CYP3A4*1G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers.CYP3A5*3 was the predominant determinant affecting tacrolimus concentration. Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers.