CYP3A4、CYP3A5和MDR1基因多态性与肾移植受者他克莫司血药浓度的关系

Association of CYP3A4,CYP3A5 and MDR1 polymorphisms with individual tacrolimus dosage regimen in renal transplant recipients

目的:研究CYP3A4*18B、CYP3A5*3及MDR1基因突变对他克莫司血药浓度/(剂量×体重)(C/D)的影响。方法:采用PCR-RFLP方法检测227例肾移植受者CYP3A4*18B、CYP3A5*3及MDR1 C1236T、G2677T/A及C3435T基因型,比较不同基因型受者之间他克莫司的C/D值的差异。结果:CYP3A4*18B和CYP3A5*3基因多态性与肾移植受者他克莫司C/D值具有相关性(P<0.01)。但是消除CYP3A5*3等位基因影响后,CYP3A4*18B各基因型间他克莫司的C/D值无显著性差异(P>0.05);而消除CYP3A4*18B等位基因影响后,CYP3A5*1/*1型和*1/*3型受者型受者他克莫司的C/D值显著性低于*3/*3(P<0.01)。MDR1各基因型组间他克莫司的C/D值均无显著性差异。结论:消除CYP3A5*3等位基因影响后,CYP3A4*18B和MDR1基因多态性对他克莫司血药浓度无影响。

Objective: To investigate the effect of CYP3A4 * 18B,CYP3A5 * 3 and MDR1 on concentration/dosage×body body weight ratios( C/D) of tacrolimus in renal transplant patients. Methodology: The CYP3A4* 18B,CYP3A5* 3,MDR1 C1236 T,G2677T/A and C3435T genotypes of 227 renal transplant patients were determined by PCRRFLP method. The differences of C/D ratios were compared among all of the genotype groups treated with tacrolimus.Results: CYP3A4* 18B and CYP3A5* 3 gene polymorphisms were associated with the C/D ratios of patients( P<0. 01).No significant association was found between C/D of tacrolimus and CYP3A4* 18B genotypes when they were classified by two CYP3A5 genotypes( P>0. 05),While after the effects of CYP3A4* 18B genotype was eliminated,the C/D ratio of tacrolimus in patients with CYP3A5* 1/* 1 and * 1/* 3 genotype group were significantly lower than those with CYP3A5* 3/* 3 genotype groups( P < 0. 01). There was no significant difference in the C/D ratio of tacrolimus among MDR1 C1236T,MDR1 G2677 T/A and MDR1 C3435 T genotype groups. Conclusion: CYP3A4 * 18B and MDR 1 gene polymorphisms do not affect blood concentration of tacrolimus.