Table 3.
Effects of genetic polymorphisms on tacrolimus dose and dose-normalized tacrolimus concentration at pre-dose and 2-hour post-dose.
| Gene | SNP | Genotype | Dose (mg)
|
C0/dose (ng/mL/mg dose)
|
C2/dose (ng/mL/mg dose)
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Median (25–75% Percentile) | P-value | N | Geometric Mean (95% CI) | P-value | N | Geometric Mean (95% CI) | P-value | ||||||
| CYP3A4 | *1B | *1/*1 | 86 | 4.0 | (3.0, 5.0) | <0.001††† | 85 | 2.50 | (2.22, 2.82) | 0.004†† | 81 | 4.49 | (3.91, 5.15) | 0.003†† |
| *1/*1B + *1B/*1B | 16 | 10.0 | (8.8, 12.0) | 16 | 1.23 | (0.80, 1.91) | 15 | 1.83 | (1.07, 3.12) | |||||
| *22 | *1/*1 | 95 | 5.0 | (3.5, 7.0) | 0.172 | 94 | 2.18 | (1.91, 2.51) | 0.213 | 89 | 3.82 | (3.24, 4.49) | 0.312 | |
| *1/*22 + *22/*22 | 7 | 4.0 | (3.5, 4.0) | 7 | 3.01 | (2.31, 3.91) | 7 | 5.16 | (3.41, 7.81) | |||||
| CYP3A5 | *3 | *1/*1 + *1/*3 | 26 | 8.5 | (3.0, 10.8) | <0.001††† | 26 | 1.20 | (0.94, 1.54) | <0.001††† | 24 | 2.09 | (1.46, 2.99) | <0.001††† |
| *3/*3 | 76 | 4.0 | (3.0, 5.0) | 75 | 2.77 | (2.46, 3.12) | 72 | 4.80 | (4.18, 5.53) | |||||
| ABCB1 | 1236C>T | C/C | 36 | 5.0 | (3.8, 8.0) | 0.440 | 36 | 2.11 | (1.63, 2.74) | 0.531 | 34 | 3.47 | (2.51, 4.81) | 0.320 |
| C/T + T/T | 66 | 4.0 | (3.3, 6.0) | 65 | 2.30 | (1.99, 2.66) | 62 | 4.16 | (3.53, 4.89) | |||||
| 2677G>T,A | G/G | 29 | 5.0 | (4.0, 10.0) | 0.064 | 29 | 2.07 | (1.49, 2.87) | 0.537 | 27 | 3.22 | (2.17, 4.77) | 0.203 | |
| G/T + G/A + T/T | 73 | 4.0 | (3.0, 6.0) | 72 | 2.30 | (2.02, 2.62) | 69 | 4.21 | (3.61, 4.90) | |||||
| 3435C>T | C/C | 25 | 5.0 | (4.0, 10.0) | 0.386 | 25 | 2.23 | (1.72, 2.90) | 0.994 | 24 | 3.53 | (2.62, 4.75) | 0.457 | |
| C/T + T/T | 77 | 4.0 | (3.0, 6.0) | 76 | 2.23 | (1.92, 2.60) | 72 | 4.03 | (3.36, 4.84) | |||||
| ABCC2 | −24C>T | C/C | 78 | 5.0 | (3.3, 6.0) | 0.873 | 77 | 2.20 | (1.87, 2.58) | 0.669 | 72 | 3.66 | (3.05, 4.38) | 0.147 |
| C/T + T/T | 24 | 4.0 | (3.8, 6.5) | 24 | 2.35 | (1.93, 2.85) | 24 | 4.74 | (3.53, 6.35) | |||||
| 1249G>A | G/G | 64 | 4.0 | (3.0, 6.0) | 0.020† | 64 | 2.53 | (2.19, 2.93) | 0.011† | 60 | 4.64 | (3.90, 5.52) | 0.003†† | |
| G/A + A/A | 38 | 5.0 | (4.0, 9.5) | 37 | 1.80 | (1.42, 2.29) | 36 | 2.92 | (2.22, 3.85) | |||||
| 3972C>T | C/C | 56 | 5.0 | (4.0, 7.3) | 0.235 | 55 | 1.96 | (1.60, 2.42) | 0.023† | 53 | 3.28 | (2.61, 4.11) | 0.012† | |
| C/T + T/T | 46 | 4.0 | (3.0, 5.8) | 46 | 2.61 | (2.28, 2.98) | 43 | 4.83 | (4.00, 5.84) | |||||
| Haplotype | Low + Reference | 71 | 4.0 | (3.0, 6.0) | 0.044† | 71 | 2.54 | (2.22, 2.90) | 0.007†† | 66 | 4.69 | (3.99, 5.51) | <0.001††† | |
| High | 31 | 5.0 | (4.0, 10.0) | 30 | 1.65 | (1.25, 2.19) | 30 | 2.60 | (1.92, 3.53) | |||||
| ABCG2 | 421C>A | C/C | 85 | 5.0 | (4.0, 6.0) | 0.094 | 84 | 2.15 | (1.89, 2.46) | 0.218 | 81 | 3.73 | (3.16, 4.41) | 0.193 |
| C/A + A/A | 17 | 4.0 | (2.0, 6.0) | 17 | 2.67 | (1.73, 4.11) | 15 | 4.93 | (3.26, 7.45) | |||||
One blood sample at pre-dose and 6 samples at 2-hour post-dose were not obtained among 102 patients. MRP2 high activity group includes H2/H2 and H1/H2; MRP2 low activity group includes H9/H9, H12/H12, H1/H9 and H1/H12); and MRP2 reference group includes H1/H1, H2/H9 and H2/H12. CYP, cytochrome P450.
ABC adenosine triphosphate-binding cassette, CYP cytochrome P450, SNP Single Nucleotide Polymorphism
†
p<0.05,
††
p<0.01,
†††
p<0.001, significant difference between groups.