Table 2.
Key study findings for Tac (not exhaustive)
| Gene | Allele/SNP | Rs number | Effect on Tac PK/PD | n | Population | Ethnicity | Reference |
|---|---|---|---|---|---|---|---|
| CYP3A4 | CYP3A4*1B CYP3A4*22 | Rs2740574 Rs35599367 | ↘ Dose-adjusted C0 for CYP3A4*1B carriers | 136 | Kidney transplant patients | Mixed (mostly Caucasian) | 64 |
| ↗ Dose requirement for CYP3A4*1B carriers | 63 | Kidney transplant patients | Caucasian | 90 | |||
| ↘ Dose-adjusted C0 for CYP3A4*1B carriers | 64 | Kidney transplant patients | Mixed | 18 | |||
| ↗ Dose-adjusted C0 for CYP3A4*22 carriers | 185 | Kidney transplant patients | Mixed | 41 | |||
| ↗ Dose-adjusted C0 for CYP3A4*22 carriers | 49 | Kidney transplant patients | Caucasian | 40 | |||
| ↗ Dose-adjusted C0 for CYP3A4*22 carriers | 60 | Pediatric heart transplant patients | Caucasian | 85 | |||
| ↘ CL/F for CYP3A4*22 carriers ↗ Dose-adjusted C0 for CYP3A4*22 carriers ↗ Dose-adjusted AUC(0,∞) for CYP3A4*22 carriers ↗ risk of supra-therapeutic exposure for CYP3A4*22 carriers ↗ Time of overexposure for CYP3A4*22 carriers ↗ Creatinine clearance for CYP3A4*22 carriers | 96 | Kidney transplant patients | Caucasian | 84 | |||
| CYP3A5 | CYP3A5*3 | Rs776746 | ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 136 | Kidney transplant patients | Mixed (mostly Caucasian) | 64 |
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↘ Dose adjusted AUC(0,12 h) for CYP3A5*1 carriers ↘ Dose adjusted C-max for CYP3A5*1 carriers | 63 | Kidney transplant patients | Caucasian | 90 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 26 | Kidney transplant patients | Caucasian | 91 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 118 | Kidney transplant patients | Chinese | 92 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 18 | Kidney transplant patients | Mixed Asian | 93 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↗ Time to achieve therapeutic C0 for CYP3A5*1 carriers | 180 | Kidney transplant patients | Mixed | 66 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↘ Dose adjusted AUC(0,12 h) for CYP3A5*1 carriers ↗ CL/F for CYP3A5*1 carriers | 134 | Kidney transplant patients | Caucasian | 94 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↘ Dose-adjusted AUC(0,12 h) for CYP3A5*1 carriers ↗ decrease in CL/F for CYP3A5*1 carriers ↘ Dose adjusted Cmax for CYP3A5*1 carriers | 50 | Kidney transplant patients | Japanese | 95 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↗ Time to achieve therapeutic C0 for CYP3A5*1 carriers | 44 | Kidney transplant patients | Mixed (mostly Caucasian) | 96 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 59 | Kidney transplant patients | Caucasian | 97 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 206 | Kidney transplant patients | Mixed | 98 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 30 | Kidney transplant patients | Chinese | 33 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↘ Dose-adjusted AUC for CYP3A5*1 carriers ↗ CLss/F for CYP3A5*1 carriers ↗ Vss/F for CYP3A5*1 carriers | 39 | Kidney transplant patients | Japanese | 99 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 24 | Kidney transplant patients | Mostly Caucasian | 100 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 64 | Kidney transplant patients | Mixed | 18 | |||
| ↗ Dose requirement for CYP3A5*1 carriers ↘ Dose-adjusted AUC(0,12 h) for CYP3A5*1 carriers | 103 | Kidney transplant patients | Chinese | 101 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 50 | Kidney transplant patients | Caucasian | 30 | |||
| ↗ CL/F for CYP3A5*1 carriers ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↘ Dose-adjusted AUC(0,12 h) for CYP3A5*1 carriers ↘ Dose adjusted Cmax for CYP3A5*1 carriers | 30 | Kidney transplant patients | Japanese | 68 | |||
| ↘ Dose-adjusted C0 for CYP3A5*1 carriers | 80 | Kidney transplant patients | Mixed (mostly Caucasian) | 67 | |||
| ↗ Dose requirement for CYP3A5*1 carriers ↘ Dose-adjusted C0 for CYP3A5*1 carriers ↗ risk of BPAR for CYP3A5*1 carriers | 1443 | Kidney transplant patients | Mixed | 76 | |||
| POR | POR*28 | Rs1057868 | ↘ Dose-adjusted C0 for POR*28 carriers expressing CYP3A5 | 298 | Kidney transplant patients | Caucasian | 89 |
| ↘ Dose-adjusted C0 for POR*28 carriers expressing CYP3A5 ↘ Dose-adjusted C0 for POR*2/*288 carriers not expressing CYP3A5 | 184 | Kidney transplant patients | Mixed | 59 | |||
| ABCB1 | 1236C>T 2677G>T/A 3435C>T | Rs1128503 Rs2032582 Rs1045642 | ↗ intra-lymphocytic concentrations for 3435T or 22677T/A variant allele carriers (recipient) | 96 | Kidney transplant patients | 87 | |
| ↗ risk of histological kidney damages/worse graft function for 3435TT donor and recipient haplotype carriers | 252 | Kidney transplant patients | 46 | ||||
| 1199G>A | Rs2229109 | ↗ intra-lymphocytic concentrations 1199A variant allele carriers (recipient) | 96 | Kidney transplant patients | 87 | ||
| ↗ Creatinine clearance for 1199A allele donor carriers | 97 | Kidney transplant patients | Caucasian | 88 |