Department of Health Statistics, School of Public Health, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Heping District, Tianjin 300070, China.
Gene. 2013 Dec 1;531(2):476-88. doi: 10.1016/j.gene.2013.09.024. Epub 2013 Sep 13.
The effect of ABCB1 C3435T SNP on the pharmacokinetics of immunosuppressive drug tacrolimus in different studies was conflicting. So a meta-analysis was employed to study the correlation of ABCB1 C3435T SNP and the pharmacokinetics of tacrolimus at different post-transplantation times.
Several studies about ABCB1 C3435T polymorphism and the pharmacokinetics of tacrolimus were collected through the search on PubMed and the Cochrane Library. After the extraction of pharmacokinetic parameters from these studies, a meta-analysis was performed on the software STATA version 11.0.
A total of 9 studies were adopted including 558 liver transplant recipients. For the dose of tacrolimus, the subjects with wild-type CC had a significantly higher tacrolimus dose than homozygous mutated genotype TT within 1 week (WMD=0.01 (0.00, 0.02), P=0.014) and the similar result in recipients with heterozygous CT compared with TT after transplantation for 1 month (WMD=0.01 (0.00, 0.02), P=0.002). For the tacrolimus concentration/dose ratio, subjects with CT had higher C/D ratio than those with CC and TT at different post-transplantation times. A subgroup analysis based on different ethnic populations was also carried out. Donors' genotypes were also considered in this meta-analysis.
Through this meta-analysis for the including studies about the pharmacokinetics of tacrolimus and ABCB1 C3435T SNP, several significant associations were obtained. Particularly, the Caucasians showed more significant associations between the C/D ratio and ABCB1 C3435T polymorphism; however, the correlations were not steady at different post-transplantation times.
不同研究中 ABCB1 C3435T SNP 对免疫抑制药物他克莫司药代动力学的影响相互矛盾。因此，进行了一项荟萃分析，以研究 ABCB1 C3435T SNP 与不同移植后时间他克莫司药代动力学的相关性。
通过在 PubMed 和 Cochrane Library 上搜索，收集了有关 ABCB1 C3435T 多态性和他克莫司药代动力学的多项研究。从这些研究中提取药代动力学参数后，在 STATA 版本 11.0 软件上进行了荟萃分析。
共纳入 9 项研究，包括 558 例肝移植受者。对于他克莫司的剂量，在 1 周内，野生型 CC 患者的他克莫司剂量明显高于纯合突变基因型 TT（WMD=0.01（0.00，0.02），P=0.014），而在移植后 1 个月时，杂合型 CT 与 TT 相比，结果类似（WMD=0.01（0.00，0.02），P=0.002）。对于他克莫司浓度/剂量比，在不同移植后时间，CT 患者的 C/D 比值高于 CC 和 TT 患者。还进行了基于不同种族人群的亚组分析。本荟萃分析还考虑了供者的基因型。
通过对包括他克莫司药代动力学和 ABCB1 C3435T SNP 在内的研究进行荟萃分析，获得了一些有意义的关联。特别是，白种人显示 C/D 比值与 ABCB1 C3435T 多态性之间存在更显著的相关性；然而，在不同的移植后时间，相关性并不稳定。
