Table 3.
Pharmacokinetic parameters of mycophenolic acid (MPA) and its glucuronide (MPAG) according to UGT or ABCC2 Single Nucleotide Polymorphisms (SNPs) in patients co-treated with tacrolimus or sirolimus
| Gene | SNP | Patients genotypes (n) | MPA dn-C0 (mg/l)/g | MPA dn-Cmax (mg/l)/g | MPA Tmax (min) | MPA dn-AUC0-12h (mg.h/l)/g | MPAG dn-C0 (mg/l) | MPAG dn- Cmax (mg/l) | MPAG Tmax (min) | MPAG dn-AUC0-9h (mg.h/l) |
|---|---|---|---|---|---|---|---|---|---|---|
| UGT1A9 | C-440T (T-331C) | CC (n=39) | 4.1±3.7 | 22.0±18.3 | 75.6±93.8 | 63.1±35.0 | 108.5±88.3 | 171.9±104.2 | 130.0±95.1 | 1143.5±692.2 |
| TC (n=27) | 4.1±2.3 | 23.3±11.3 | 68.5±97.4 | 68.7±30.1 | 95.0±50.6 | 144.7±59.0 | 111.5±76.5 | 974.3±429.7 | ||
| TT (n=4) | 4.4±2.1 | 29.0±6.7 | 25.0±10.0 | 61.5±17.7 | 102.2±46.6 | 174.7±86.4 | 77.5±35.0 | 1163.1±559.7 | ||
| p values | 0.5049 | 0.0753 | 0.0330 | 0.5080 | 0.7807 | 0.7867 | 0.3018 | 0.6777 | ||
| T-275A or C-2152T* | TT(CC) (n=63) | 4.3±3.1 | 23.3±15.8 | 71.9±97.2 | 65.7±30.4 | 105.8±69.8 | 163.4±90.4 | 118.4±88.9 | 1090.6±605.2 | |
| TA (CT) (n=7) | 2.8±2.8 | 19.3±11.7 | 52.8±22.1 | 60.3±51.2 | 79.7±50.6 | 144.9±69.9 | 132.8±59.6 | 978.2±523.4 | ||
| p values | 0.0912 | 0.3325 | 0.8469 | 0.1799 | 0.5119 | 0.9143 | 0.2858 | 0.9143 | ||
| T98C | TT (n=68) | 4.1±3.0 | 23.3±15.4 | 70.1±93.8 | 66.2±32.5 | 103.7±68.9 | 163.4.2±88.7 | 119.0±87.2 | 1089.2±599.4 | |
| TC (n=2) | 6.1±6.5 | 8.9±3.1 | 65.0±35.3 | 30.9±8.7 | 78.9±38.3 | 98.0±51.0 | 150.0±42.4 | 745.6±371.3 | ||
| p values | 0.5671 | 0.0344 | 0.5957 | 0.0570 | 0.6764 | 0.2172 | 0.2358 | 0.4175 | ||
| UGT1A8 | C518G | CC (n=40) | 4.2±3.2 | 25.4±18.1 | 69.0±94.5 | 66.8±29.6 | 105.1±75.5 | 166.8±95.4 | 109.7±73.8 | 1066.9±587.5 |
| CG (n=26) | 4.5±3.0 | 21.0±9.8 | 73.5±97.8 | 67.9±36.8 | 105.1±60.9 | 160.7±41.9 | 139.6±105.6 | 1040.4±643.9 | ||
| GG (n=4) | 1.1±0.4 | 10.1±6.0 | 57.5±28.7 | 30.9±8.3 | 68.4±30.5 | 114.2±41.8 | 92.5±37.7 | 807.7±263.5 | ||
| p values | 0.0130 | 0.0368 | 0.4694 | 0.0171 | 0.5331 | 0.5350 | 0.5786 | 0.6701 | ||
| ABCC2 | C-24T | CC (n=48) | 4.1±3.2 | 22.7±17.6 | 60.4±51.6 | 64.1±33.0 | 98.4±72.5 | 158.1±93.7 | 127.1±78.0 | 683.1±299.7 |
| CT (n=19) | 4.7±3.0 | 23.0±9.8 | 96.8±157.5 | 67.4±33.6 | 112.8±60.1 | 165.1±75.9 | 103.15±110.05 | 1107.0±648.1 | ||
| TT (n=3) | 2.6±1.2 | 26.2±4.7 | 53.3±11.5 | 68.0±27.7 | 116.2±49.4 | 193.9±95.4 | 110.0±17.3 | 1341.8±577.8 | ||
| p values | 0.5066 | 0.1804 | 0.7746 | 0.8393 | 0.3411 | 0.2371 | 0.0913 | 0.3835 | ||
*
SNPs in complete linkage disequilibrium