Correlation of CYP3A5 * 3 gene polymorphisms with sirolimus blood concentration in Chinese stable renal transplant recipients

Abstract

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. Key words: Sirolimus; Polymorphism, single nucleotide; Cytochrome P-450 CYP3A5; Kidney transplantation