Table 4.
Impact of selected CYP3A4/5 and ABCB1 variants on acute rejection, delayed graft function and estimated glomerular filtration rate at discharge (multivariate regression analysis).
| Gene | Variant | Genetic Model | Acute Rejection | Delayed graft function | eGFR# | |||
|---|---|---|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | Effect (95% CI) |
P value | |||
| CYP3A4 | *1B, T>C rs2740574 |
dominant: TC vs TT |
1.42 (0.21, 9.38) | 0.72 | 2.39 (0.49, 11.55) | 0.28 | -0.29 (-1.26, 0.68) |
0.56 |
| log additive: 0,1,2 | 1.42 (0.21, 9.38) | 0.72 | 2.39 (0.49, 11.55) | 0.28 | -0.29 (-1.26, 0.68) |
0.56 | ||
| CYP3A4 | *22, G>A rs35599367 |
dominant: GA vs GG |
1.79 (0.24, 13.83) | 0.58 | 0.89 (0.15, 5.23) | 0.89 | 0.15 (-0.79, 1.1) | 0.75 |
| log additive: 0,1,2 | 1.79 (0.24, 13.83) | 0.58 | 0.89 (0.15, 5.23) | 0.89 | 0.15 (-0.79, 1.1) | 0.75 | ||
| CYP3A5 | *3, T>C rs776746 |
dominant: TT + TC vs CC |
1.78 (0.43, 7.32) | 0.43 | 2.07 (0.58, 7.38) | 0.26 | -0.73 (-1.50, 0.05) |
0.068 |
| log additive: 0,1,2 | 1.76 (0.43, 7.18) | 0.44 | 2.18 (0.69, 6.87) | 0.18 | -0.74 (-1.45, -0.04) |
0.042+ | ||
| CYP3A | CYP3A4/5 combined genotypes† |
dominant: IM + PM vs EM |
0.46 (0.11, 1.98) | 0.31 | 0.47 (0.13, 1.69) | 0.25 | 0.82 (0.02, 1.61) | 0.046+ |
| log additive: EM = 0, IM = 1, PM = 2 | 0.82 (0.24, 2.76) | 0.74 | 0.61 (0.22, 1.70) | 0.34 | 0.45 (-0.12, 1.03) | 0.12 | ||
| ABCB1 | 1236C>T rs1128503 |
dominant: CT + TT vs CC |
1.54 (0.41, 5.83) | 0.52 | 1.44 (0.53, 3.90) | 0.47 | -0.03 (-0.63, 0.58) | 0.94 |
| log additive: 0, 1, 2 | 1.22 (0.54, 2.75) | 0.63 | 1.18 (0.62, 2.25) | 0.61 | 0.00 (-0.39, 0.39) | 1 | ||
| ABCB1 | 2677G>T/A## rs2032582 |
dominant: GT + TT vs GG |
7.38 (1.07, 51.05) | 0.016+ | 1.23 (0.43, 3.47) | 0.70 | -0.18 (-0.80, 0.44) | 0.57 |
| log additive: 0, 1, 2 | 1.8 (0.75, 4.29) | 0.18 | 0.97 (0.49, 1.94) | 0.93 | -0.13 (-0.53, 0.28) | 0.54 | ||
| ABCB1 | 3435C>T rs1045642 |
dominant: CT + TT vs CC |
5.06 (0.84, 30.52) | 0.043+ | 1.95 (0.63, 6.02) | 0.24 | -0.38 (-1.01, 0.25) | 0.24 |
| log additive: 0, 1, 2 | 2.14 (0.91, 5.04) | 0.071 | 0.90 (0.46, 1.74) | 0.75 | -0.12 (-0.51, 0.26) | 0.53 | ||
| ABCB1 | TTT haplotype (1236,2677,3435) | dominant: carriers vs non-carriers |
2.2 (0.6, 8.06) | 0.22 | 1.62 (0.61, 4.29) | 0.33 | -0.27 (-0.85, 0.32) | 0.37 |
| log additive: 0, 1, 2 | 2.2 (0.6, 8.06) | 0.22 | 1.62 (0.61, 4.29) | 0.33 | -0.27 (-0.85, 0.32) | 0.37 | ||
eGFR, estimated glomerular filtration rate at discharge, OR, odds ratio, CI, confidence interval, Multivariate analysis includes HLA mismatch <3 alleles vs. ≥3 alleles, % panel reactive antibodies: ≤10% (low risk) vs >10% (high risk), AB0 compatibility: yes vs. no, previous transplantation: yes vs. no, living vs. deceased donor, basiliximab vs. thymoglobulin, valgancyclovir yes vs. no.
# Square root transformed eGFR value.
## The A allele was combined with T allele previous to statistical analysis, i.e. GA carriers were treated as GT carriers and TA carriers as TT carriers.
+ Not significant after correction for multiple comparisons.
† According to Elens et al., 2013, Lloberas et al, 2017.