The effect of ABCB1 polymorphism on sirolimus in renal transplant recipients: a meta-analysis
Bibliographic record
Abstract
Background: Sirolimus (SRL) is an immunosuppressive drug and substrate of the P-glycoprotein (P-GP) encoded by ABCB1. The relationship between ABCB1 polymorphism and the pharmacokinetics of SRL in different studies were conflicting in renal transplant recipients. Thus, this meta-analysis aims to investigate the influence of ABCB1 C3435T, C1236T, and G2677T/A polymorphisms on the dose-adjusted trough level (C/D) of SRL in renal transplant recipients. Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies. The quality of each eligible study was assessed according to Newcastle-Ottawa Scale. The STATA 15.0 was adopted to perform the meta-analysis. The fixed-effects model was used for pooled results with low heterogeneity (I2 ≤50%); otherwise, the random-effects model was used. Results: A total of 6 studies were included in the meta-analysis. Results of pooled analysis showed no significant association of SRL C/D ratio with ABCB1 C3435T polymorphism. The subgroup analysis based on different ethnic groups and different time-points after SRL initiation in renal transplant recipients were also conducted. No significant association was observed in these subgroups. Significant associations were showed between ABCB1 C1236T polymorphism and the C/D ratio of SRL in the homozygous model (TT vs. CC; WMD: −45.54; 95% CI: −75.15, −15.94; P=0.003), and also in subgroup of Caucasian (TT vs. CC; WMD: −46.57; 95% CI: −91.90, −1.25; P=0.044 and TT vs. CC + CT; WMD: −52.10; 95% CI: −95.38, −8.82; P=0.018). Significant differences were found in association between the ABCB1 G2677T/A polymorphism and the C/D ratio of SRL, including the homozygous model (TT vs. GG; WMD: −76.47; 95% CI: −126.37, −26.58; P= 0.003), the heterozygous model (GT vs. GG,WMD: 178.62; 95% CI: 125.03, 232.22; P= 0.000), the dominant model (GT + TT vs. GG; WMD: 82.23; 95% CI: 36.28, 128.17; P=0.000), the recessive model (TT vs. GG + GT; WMD: −179.38; 95% CI: −283.33, −75.42; P=0.001), and the over-dominant model (GT vs. GG + TT; WMD: 199.44; 95% CI: 84.84, 314.05; P=0.001). Conclusions: No significant association exists between ABCB1 C3435T polymorphism and the C/D ratio of SRL in renal transplant recipients. To achieve target therapeutic concentrations, ABCB1 C1236T homozygous mutant TT genotype will require a higher dose of sirolimus than wild type GG, especially in Caucasian renal transplant recipients. ABCB1 G2677T/A TT genotype will also need a higher dose of sirolimus genotype. Genotyping of ABCB1 might help to improve the individualization of SRL for renal transplant recipients. Further studies are expected to provide high-quality evidence.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.014 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.054 |
| Bibliometrics | 0.004 | 0.006 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".