CAJ | 학술논문

目的探讨中国汉族稳定期肾移植受者CYP3A5*3和MDR1C3435T基因多态性与血西罗莫司浓度的相关性及个体间差异的影响因素.方法以112例中国汉族稳定期肾移植受者为研究对象,记录受者性别、年龄、身高、体质量等,采用直接测序法检测CYP3A5*3和MDR1C3435T基因型,化学发光微粒子免疫检测法测定全血西罗莫司浓度谷值(C0).研究血西罗莫司浓度个体间差异的影响因素,比较CYP3A5*3和MDR1C3435T不同基因型受者间血西罗莫司浓度的差异.结果 112例中,CYP3A5*1/*1型10例,*1/*3型49例,*3/*3型53例,*1、*3等位基因的出现频率分别为30.81％和69.19％.MDR13435CC型31例,CT型60例,TT型21例,C、T等位基因的出现频率分别为54.46％和45.54％.受者CYP3A5*3基因型是血西罗莫司浓度的主要影响因素(P=0.000),性别、年龄、身高、术后时间、血肌酐、血红蛋白、联合应用环孢素A和MDR1C3435T基因型对血西罗莫司浓度均无影响(P＞0.05).*1/*1型受者C0·剂量-1·体质量-1为(0.0721±0.0202)μg·L-1·mg-1·kg-,*1/*3型受者为(0.1055±0.0395)μg· L-1 ·mg-1 ·kg-1,*3/*3型受者为(0.1395±0.0537)μg·L-1·mg-1 ·kg-1(P＜0.01).不同基因型受者C0·剂量-1·体质量-1的关系为*3/*3型＞*1/*3型＞*1/*1型,*1/*3型受者是*1/*1型的1.46倍,*3/*3型受者是*1/*1型的1.93倍.结论汉族稳定期肾移植受者的CYP3A5*3基因多态性是其血西罗莫司浓度的主要影响因素,MDR1C3435T基因多态性则对其无影响.与CYP3A5* 3/*3型受者相比较,CYP3A5* 1/*1、*1/*3型受者为达到目标血药浓度需服用更高剂量的西罗莫司.
목적 탐토중국한족은정기신이식수자CYP3A5*3화MDR1C3435T기인다태성여혈서라막사농도적상관성급개체간차이적영향인소.방법 이112례중국한족은정기신이식수자위연구대상,기록수자성별、년령、신고、체질량등,채용직접측서법검측CYP3A5*3화MDR1C3435T기인형,화학발광미입자면역검측법측정전혈서라막사농도곡치(C0).연구혈서라막사농도개체간차이적영향인소,비교CYP3A5*3화MDR1C3435T불동기인형수자간혈서라막사농도적차이.결과 112례중,CYP3A5*1/*1형10례,*1/*3형49례,*3/*3형53례,*1、*3등위기인적출현빈솔분별위30.81％화69.19％.MDR13435CC형31례,CT형60례,TT형21례,C、T등위기인적출현빈솔분별위54.46％화45.54％.수자CYP3A5*3기인형시혈서라막사농도적주요영향인소(P=0.000),성별、년령、신고、술후시간、혈기항、혈홍단백、연합응용배포소A화MDR1C3435T기인형대혈서라막사농도균무영향(P＞0.05).*1/*1형수자C0·제량-1·체질량-1위(0.0721±0.0202)μg·L-1·mg-1·kg-,*1/*3형수자위(0.1055±0.0395)μg· L-1 ·mg-1 ·kg-1,*3/*3형수자위(0.1395±0.0537)μg·L-1·mg-1 ·kg-1(P＜0.01).불동기인형수자C0·제량-1·체질량-1적관계위*3/*3형＞*1/*3형＞*1/*1형,*1/*3형수자시*1/*1형적1.46배,*3/*3형수자시*1/*1형적1.93배.결론 한족은정기신이식수자적CYP3A5*3기인다태성시기혈서라막사농도적주요영향인소,MDR1C3435T기인다태성칙대기무영향.여CYP3A5* 3/*3형수자상비교,CYP3A5* 1/*1、*1/*3형수자위체도목표혈약농도수복용경고제량적서라막사.
Objective To investigate the effect of CYP3A5 * 3 and MDR1C3435T polymorphisms on the blood trough concentration of sirolimus in the Chinese renal transplantation recipients with stable renal function and the influencing factors for individual differences.Method 112 cases of Chinese renal transplantation recipients with stable renal function were recruited in this study.Related data of the recipients,including gender,age,height and body mass,were recoded.CYP3A5 and MDR1 genotypes were determined by the direct sequencing.Blood trough concentration of sirolimus was measured by using chemiluminescence microparticle immuno assay (CMIA).The influencing factors of individual differences in sirolimus blood trough concentration was analyzed,and the correlation of CYP3A5 * 3 and MDR1C3435T gene polymorphisms with sirolimus blood trough concentration was evaluated.Result Of the 112 cases,there were 10 cases (8.93％) of CYP3A5 * 1/* 1,49 cases (43.75％) of CYP3A5 * 1/* 3,and 53 cases (47.32％) of CYP3A5 * 3/* 3.Allele frequencies of CYP3A5 * 1 and * 3 were 30.81％ and 69.19％,respectively.There were 31 recipients (27.68％) with MDR1 3435CC,60 (53.57％) with MDR1 3435CT,and 21 (18.75％) with MDR1 3435TT.Allele frequencies for C and T at position 3435 of MDR1 were 54.46％ and 45.54％,respectively.In this study,recipients' CYP3A5 * 3 genotype was the main factor (P =0.000) of sirolimus blood trough concentration,but dose,gender,age,height,postoperative time,the level of serum creatinine,hemoglobin levels,combined use of CsA and MDR1C3435T genotype had no effects on sirolimus blood trough concentration (P ＞ 0.05).sirolimus blood trough concentration/(dose weight) in * 1/* 1,* 1/* 3 and * 3/* 3 recipients was (0.0721 ± 0.0202),(0.1055 ± 0.0395),and (0.1395 ± 0.0537) μg·L-1 ·mg-1 ·kg-1,respectively,The sirolimus blood trough concentration/ (dose weight) in * 1/* 3 recipients was 1.46 times higher than that in * 1/* 1 recipients,and that in * 3/* 3 recipients were 1.93 times higher than that in * 1/* 1 recipients.There was significant difference in sirolimus blood trough concentration/(dose weight) between recipients with different CYP3A5 * 3 genotypes (P =0.000).Conclusion The CYP3A5 * 3 gene polymorphism is closely related to the blood trough concentration/dose of sirolimus,and is the main factor of the blood trough concentration of sirolimus between individuals.