Table 1.
Summary of discussed pharmacogenetic variants related to pharmacokinetics of kidney transplant immunosuppression*
| Drug | Genotype (rs number) | Phenotype | Reference |
|---|---|---|---|
| Tacrolimus | CYP3A5*3 (rs776746) | *3 homozygotes (CYP3A5 non-expressers) have higher dose-adjusted trough blood concentrations and lower dose requirements compared to *1 carriers; evaluated in a randomized control trial with no effect on 3 month outcomes | (13–24, 36) |
|
ABCB1 3435C>T (rs1045642) 2677G>A/T (rs2032582) 1236C>T (rs1128503) |
No clear effect on pharmacokinetics | (23, 27) | |
| CYP3A4*22 (rs35599367) | May explain additional variability in dose-adjusted blood concentration in combination with CYP3A5*1/*3 | (22, 23, 29–31) | |
| POR*28 (rs1057868) | Associated with lower dose-adjusted blood concentration but only in CYP3A5 expressers | (21, 32–34) | |
| PPARA (rs4253728 and rs4823613) | Associated with dose adjusted blood concentration but results conflicting | (21, 35) | |
|
| |||
| Cyclosporine | CYP3A5*3 (rs776746) | No clear effect on pharmacokinetics | (13) |
|
ABCB1 3435C>T (rs1045642) 2677G>A/T (rs2032582) 1236C>T (rs1128503) |
No clear effect on pharmacokinetics | (27) | |
| CYP3A4*22 (rs35599367) | Associated with higher dose-adjusted blood concentration | (21, 29, 30) | |
| POR*28 (rs1057868) | Associated with lower dose-adjusted blood concentration in CYP3A5 non-expressers | (32) | |
|
| |||
| Mycophenolate | UGT1A9 (rs6714486) (rs17868320) | Associated with lower MPA exposure | (8, 37) |
|
| |||
| Sirolimus | CYP3A5*3 (rs776746) | Associated with higher dose-adjusted blood concentration | (38) |
|
| |||
| Everolimus | CYP3A5*3 (rs776746) | No clear effect on pharmacokinetics | (30, 39) |
*
List not exhaustive of all published literature but reflects recent publications or well established relationships
Abbreviations: MPA, mycophenolic acid