Dissertation
Dissertation > Medicine, health > Pharmacy > Pharmacology

Correlation of CYP3A5*3, MDR1C3435T Gene Polymorphisms with Sirolimus Blood Concentration in Chinese Stable Renal Transplant Recipients

Author LiaoZuo
Tutor FengDuanHao
School Hebei North University
Course Pharmacology
Keywords CYP3A5 MDR1 gene polymorphisms sirolimus bloodtrough concentraotion renal transplantation
CLC R96
Type Master's thesis
Year 2013
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The study investigated the effect of CYP3A5*3and MDR1C3435T polymorphisms on the blood trough concentration of sirolimus in the Chinese renal transplant recipients with stable renal function and analyse the influence factors of sirolimus blood trough concentration individual’s differences.112cases of Chinese renal transplant recipients with stable renal function were recruited in this study. Related data of the recipients, such as gender, age, height and body mass, were recorded. CYP3A5and MDR1genotypes were determined by the direct sequencing. Blood trough concentration of sirolimus was measured by MEIA. Analyse the influence factors of sirolimus blood trough concentration of individual’s differences and evaluate the correlation of CYP3A5*3MDR1C3435T gene polymorphism with sirolimus blood trough concentration.Of the112cases,10patients (8.93%) were CYP3A5*1/*1,49(43.75%) CYP3A5*1/*3, and53(47.32%) CYP3A5*3/*3. Allele frequencies of CYP3A5*1and*3were30.81%and69.19%, respectively. There was31recipients(27.68%) with MDR13435CC,60(53.57%) with MDR13435CT,21(18.75%) with MDR13435TT. Allele frequencies for C and T at position3435of MDR1were54.46%and45.54%, respectively. In this study, recipients’CYP3A5*3genotype and ALT were the main factors with the sirolimus blood trough concentration/dose. Gender, age, height, body mass, postoperative time, lipid, serum creatinine, hemoglobin, CsA combination and MDRlC3435T genotype were found to have no correlation.CYP3A5*1/*1patients sirolimus blood trough concentration/(dose.weight) were (0.0721±0.0202) ng·ml-1·mg-1·kg-1,*1/*3patients (0.1055±0.0395)ng·ml-1·mg-1·kg-1,*3/*3patients(0.1395±0.0537) ng·ml-1·mg-1·kg-1,the relationship of sirolimus blood trough concentration/(dose·weight)between patients with different genotypes were*3/*3>*1/*3>*1/*1recipients.*1/*3recipients were1.46times to*1/*1recipients.*3/*3recipients1.93times to*1/*1recipients.Recipients with different CYP3A5*3genotypes sirolimus blood trough concentration/(dose·weight)were significant(P=0.000).CYP3A5*1/*1patients sirolimus blood trough corlcentration/dose were(4.8012±1.3343)ng·m1-1·mg-1,*1/*3patients (6.8059±2.3448) ng·ml·.mg’,*3/*3patients (9.1291±3.1475)ng·ml-1·mg-1,the relationship of sirolimus blood trough concentration/dose between patients with different genotypes were*3/*3>*1/*3>*1/*1recipients.*1/*3recipients were1.42times to*1/*1recipients.*3/*3recipients1.90times to*1/*1recipients.Recipients with different CYP3A5*3genotypes sirolimus blood trough concentration/dose were significant(P=0.000).CYP3A5*1/*1patients sirolimus blood trough concentration/(dose·SA) were (2.7629±0.7611)ng·ml-1·mg-1·m-2,*1/*3patients (3.9883±1.4188) ng·m1-1·mg-1·m-2,*3/*3patients (5.2899±1.8664) ng·m1-1·mg-1·m-2, the relationship of sirolimus blood trough concentration/(dose·SA)between patients with different genotypes were*3/*3>*1/*3>*1/*1recipients.*1/3recipients were1.44times to*1/*1recipients.*3/*3recipients1.91times to*1/*1recipients. Recipients with different CYP3A5*3genotypes sirolimus blood trough concentration/(dose·SA)were significant (P=0.000).Chinese renal transplant recipients with stable renal function, CYP3A5*3gene polymorphism and blood trough concentration of sirolimus are closely related. In order to achieve the similar blood trough concentration, the patients with CYP3A5*1/*1and*1/*3gene type need more dose of sirolimus than CYP3A5*3/*3. CYP3A5*3gene polymorphism and liver function are the main reasons for the difference of sirolimus dosage and concentration between individuals. The evaluation of the CYP3A5*3polymorphism of the recipients may be helpful in personalized use of sirolimus.

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