摘要
目的探讨细胞色素P4503A5（CYP3A5）＊1和CYP3A5＊3基因型对肾移植受者他克莫司药物剂量的影响。方法单中心肾移植后服用他克莫司的受者69例，移植后1和2个月采集受者外周血，提取DNA，用序列特异性引物聚合酶链反应技术检测受者的CYP3A5基因分型。统计不同基因型受者肾移植后l和2个月时的他克莫司剂量，计算血他克莫司浓度／N量（C／D值）。结果69例中，CYP3A5＊1／＊1基因型6N（8．7％），CYP3A5＊1／＊3基因型22例（31．9oA），CYP3A5＊3／＊3基因型41例（59．4%）。移植后1和2个月时，CYP3A5＊1基因型受者他克莫司剂量显著高于CYP3A5＊3／＊3型受者（均为P〈0．0001）；CYP3A5＊1基因型受者血他克莫司浓度低于CYP3A5＊3／＊3型受者（P=0．0208，P=0．0191）。CYP3A5＊1基因型受者在移植后1个月的C／D值显著低于CYP3A5＊3／＊3型受者（P〈0．0001）；CYP3A5＊1基因型的受者在移植后2个月的C／D值也显著低于CYP3A5＊3／＊3型受者（P=0．0191）。受者的肝、肾功能对移植后1和2个月的C／D埴无显著影响。性别对他克莫司的剂量无影响。结论携带CYP3A5＊1基因型的受者与CYP3A5＊3／＊3型受者相比较，需要更高的他克莫司剂量才能达到目标血药浓度。
Objective To study the effects of CYP3A5 ＊ 1 and CYP3A5 ＊ 3 genotypes on tacrolimus dose requirement. Method We tested archival peripheral blood of 69 kidney recipients for CYP3A5 genotyping by polymerase chain reaction. The dose, blood concentrations and dose-normalized blood concentrations of tacrolimus were measured at 1st and 2nd month after the renal transplantation. Result There were 6 cases of CYP3A5 ＊ 1/＊1 （8. 7%）, 22 cases of CYP3A5＊ 1/＊3 （31.9%）, and 41 cases of CYP3A5 ＊ 3/＊ 3 （59. 4%）. At 1st and 2nd month after the renal transplantation, the carriers of CYP3A5＊1 genotype had a higher mean tacrolimus dose than CYP3A5 ＊ 3/＊ 3 genotye （both P〈0. 0001）, and those of CYP3A5 ＊ 1 genotype had lower mean tacrolimus concentrations than CYP3A5 ＊ 3/＊ 3 genotye （P = 0. 020 8, and P = 0. 019 1 respectively）. Meanwhile, the carriers of CYP3A5 ＊ 1 genotype had lower dose-normalized blood concentrations of tacrolimus than CYP3A5 ＊ 3/＊ 3 genotye （P〈0.0001） at 1st month after the renal transplantation, as well as at 2nd month after the renal transplantation （P = 0. 019 1）. Hepatic and renal function showed no significant effect on tacrolimus dose adjusted concentration at 1st and 2nd month after transplantation. Gender did not show a significant impact on tacrolimus dose.Conclusion CYP3A5 ＊ 1 carriers needhigher tacrolimus dose than CYP3A5 ＊ 3 homozygote to achieve the target blood concentration. CYP3A5 genotyping is a new approach for detecting tacrolimus dose requirement in kidney recipients.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2014年第1期25-28,共4页
Chinese Journal of Organ Transplantation
