孕烷X受体基因多态性与中国肾移植受者他克莫司浓度/剂量比值的相关性  

Correlation between genetic polymorphism of pregnane X receptor and ratio of tacrolimus concentration/dose in patients with renal transplantation

作　　者：陈启晨 胡正威[1] 王威[1] 李清[1] 刘克锋[1] 田鑫[1] 

机构地区：[1]郑州大学第一附属医院药学部,郑州450052

出　　处：《中国临床药理学杂志》2016年第17期1557-1560,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(U1504831);郑州大学国家级大学生创新创业训练计划基金资助项目(2015XJXM299)

摘　　要：目的观察孕烷X受体(PXR)的基因多态性对肾移植术后患者服用他克莫司浓度/剂量比值(C/D)的影响。方法收集记录57例肾移植受者的血液样本,用Sequenom Mass Array系统基因分型方法对患者进行基因分型,比较不同基因型患者之间他克莫司C/D值的差异。结果在PXR rs3814055各基因型中,CC型、CT型和TT型患者的C/D值分别为(108.87±58.34),(165.23±121.79),(284.79±254.83)ng·mL^(-1)·kg·mg^(-1),差异有统计学意义(P<0.05)。在PXR rs2276707各基因型中,CC型、CT型和TT型患者的C/D值分别为(83.68±28.49),(151.14±114.28),(164.97±129.12)ng·mL^(-1)·kg·mg^(-1),差异有统计学意义(P<0.05)。在PXR rs6785049各基因型中,GG型、AA+AG型患者的C/D值分别为(159.58±131.05),(132.87±100.49)ng·mL^(-1)·kg·mg^(-1),差异无统计学意义(P>0.05)。将PXR rs2276707与PXR rs6785049进行基因型组合分析,在CC-AA基因型组、CT-AG基因型组和TT-GG基因型组患者的C/D值分别为(78.12±20.97),(157.56±117.03),(169.48±136.09)ng·mL^(-1)·kg·mg^(-1),差异无统计学意义(P<0.05)。结论 PXR rs3814055和PXR rs2276707基因多态性对他克莫司的C/D值有影响,PXR rs6785049对C/D值无明显影响。肾移植受者用药前进行PXR rs3814055、PXR rs2276707基因型的检测,有利于指导他克莫司的个体化用药。Objective The study aims to investigate the effect of preg- nane X receptor （PXR） polymorphisms on tacrolimus concentrations/ dosage ratio （ C/D ） in Chinese renal transplanted recipients. Methods Totally 57 renal transplanted recipients were recruited. Their genotypes were determined by Sequenom MassArray methods, then the differences of tacrolimus C/D among the patients with different genotypes were compared. Results Among the genotypes of PXR rs3814055, the C/D ratio in type CC, CT and rlT were （ 108.87 ± 58. 34）, （ 165.23 ±121.79） ,（284. 79 ± 254. 83）ng·mL-1 · kg·mg-1 respectively, with significant difference （ P 〈 0.05 ） . Among the genotypes of PXR rs2276707, the C/D ratio in type CC, CT and 3T were （83. 68 ± 28.49）,（151.14±14.28）, （164.97±29.12） ng·mL-1 · kg·mg-1 respectively, with significant difference （P 〈 0. 05）. Among the genotype of PXR rs6785049, there were no significantly differences between the C/D ratio of homozygous wild type GG recipients [ （159.58 ±131.05） ng·mL-1 · kg·mg-1] and the ratios of heterozygous mutant GA and homozygous mutant AA recipients [ （132. 87 ±100.49） ng·mL-1 · kg·mg-1] （ P 〉 0.05 ）. In combinational analysis of PXR rs2276707 and PXR rs6785049 genotype, the C/D ratio of patients with CC - AA genotype, CT - AG genotype and TF - GG genotype were （78.12 ±0.97）, （157.56 ± 117.03）, （ 169.48 ± 136. 09 ）ng·mL-1 · kg·mg-1 respectively, with significant difference （ P 〈 0.05 ）. Conclusion The study shows that genetic polymorphisms of PXR rs3814055 and PXR rs2276707 may be responsible for C/D ratio of tacrolimus. Detecting the PXR rs3814055 and PXR rs2276707 genotypes of renal transplanted recipients before treat- ment is beneficial to the individualized medication of tacrolimus.

关 键 词：肾移植 他克莫司 rs3814055 rs2276707 rs6785049 基因多态性 

分 类 号：R97[医药卫生—药品]