PXR2基因多态性对肾移植术后他克莫司血药浓度和药物服用剂量的影响

Effect of PXR2 polymorphism on the rate of tacrolimus blood concentration and drug dose in renal transplant patients

目的:探究孕烷受体(pregnane X receptor,PXR)的剪接变体PAR-2(PXR2)启动子区6 bp-deletion基因多态性对肾移植术后他克莫司血药浓度和药物服用剂量(blood concentration and drug dose,C/D)影响,从而指导患者肾移植术后他克莫司的个体化治疗。方法:收集江西省人民医院器官移植科2014年7月至2018年6月73例肾移植患者血液标本,采用Anelic Special-Touch Down PCR法检测PXR2基因多态性分型。记录患者年龄、性别、体重、血红蛋白、总胆红素值及质子泵抑制剂的使用情况。结果:PCR结果显示,73例标本中PXR2纯合子型39例(53.42%),野生型4例(5.48%),杂合子型30例(41.1%)。多元线性回归分析显示,PAR-2启动子区6 bp-deletion基因多态性的基因分型与C/D无明显相关性,差异无统计学意义(P>0.05)。血红蛋白、总胆红素与C/D呈正相关,差异有统计学意义(P<0.05)。单因素方差分析显示,纯合子型、野生型、杂合子型3个组别的C/D数值在术后3 d、2周、1个月组间比较,差异均无统计学意义(P>0.05)。结论:PXR-2启动子区6 bp-deletion基因多态性对他克莫司C/D无影响,血红蛋白、胆红素水平对他克莫司C/D有影响且呈正相关。

Objective: To Explore effect of PAR-2 splice variant of PXR (PXR2) polymorphism on the rate of tacrolimus blood concentration and drug dose (C/D) in renal transplant patients. Methods: We collected the 73 blood preparations of the renal transplant patients in the Organ Transplant Department of Jiangxi Province People’s Hospital from July 2014 To June 2017. Detected the PXR2 polymorphism by the means of Anelic Special- Touch Down PCR. Recorded the age, sexual, weight, hemoglobin value, total bilirubin value and the use of proton-pump inhibitor. Results: The PCR show that there are three genes types which include 39 homozygote type (53.42%), 4 wild type (5.48%) and 30 heterozygote type (41.1%). The multiple linear regression shows that the 6 bp-deletion polymorphism in the promotor region of PXR2 is unrelated to C/D, and the difference was not statistically significant (P>0.05). The hemoglobin value and total bilirubin value was changing positively with the tacrolimus C/D and the difference was statistically significant (P<0.05). The One-Way ANOVA indicated that there was no statistically significant difference of C/D values between the three groups of homozygous, wild and heterozygous types on 3 days, 2 weeks and 1 month after the operation. Conclusion: The 6 bp-deletion polymorphism in the promotor region of PXR2 had nothing to do with Tacrolimus C/D. The hemoglobin value and total bilirubin value was changing positively with the Tacrolimus C/D.