中文摘要：

高度可变的 pharmacokinetics 和 tacrolimus (TAC ) 的狭窄的治疗学的窗户妨碍了它的临床的使用。基因多型性可以贡献可变反应，但是证据是不引人注目的，并且解释是不清楚的。在我们试图发现以前未知的基因因素的这研究，那可以影响 TAC 剂量要求。有 TAC 调整剂量的集中(C0/D ) 的 105 小径相关的单个核苷酸多型性(SNP ) 的协会在在 382 中国肾操作以后的 7， 30 和 90 d 被检验移植接受者。在 CYP3A5 non-expressers，带 IL-3 rs181781 AA 遗传型的病人在 30 和 90 d 与 AG 遗传型比那些显示出显著地更高的 TAC logC0/D 操作以后(AA 对 AG， 2.21 吗？？

英文摘要：

The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus （TAC） has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms （SNPs） with TAC dose-adjusted concentrations （CO/D） was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients. In CYP3A5 non-expressers, the patients carrying the IL-3 rs181781 AA genotype showed a significantly higher TAC IogCO/D than those with the AG genotype at 30 and 90 d post-operation （AA vs AG, 2.21±0.06 vs 2.01±0.03, P=0.004; and 2.17±0.06 vs 2.03±0.03, P=0.033, respectively）, and than those with the GG genotype at 30 d （AA vs GG, 2.21±0.06 vs 2.04±0.03, P=0.011）. At 30 d, the TAC IogCO/D in the grouped AG＋GG genotypes of CTLA4 rs4553808 was significantly lower than that in the AA genotype （P=0.041） in CYP3A5 expressers, but it was higher （P=0.008） in the non-expressers. We further validated the influence of CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437 on the TAC CO/D; other candidate SNPs were not associated with the differences in TAC CO/D. In conclusion, genetic polymorphisms in the immune genes IL-3 rs181781 and CTLA4 rs4553808 may influence the TAC CO/D. They may, together with CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437, contribute to the variation in TAC dose requirements. When conducting individualized therapy with tacrolimus, these genetic factors should be taken into account.