单核苷酸多态性对他克莫司在伊朗西北部肾移植受者体内药代动力学的影响。

IF 3.1 Q2 PHARMACOLOGY & PHARMACY
Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan
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引用次数: 0

摘要

目的:钙调磷酸酶抑制剂(CNIs)如他克莫司是肾移植后主要的免疫抑制药物,可抑制细胞因子的表达。这些药物的药代动力学受细胞色素P450 (CYP)酶、多药耐药-1 (MDR-1)和C25385T妊娠X受体(PXR)的影响。本研究旨在探讨这些基因的单核苷酸多态性(SNP)对他克莫司剂量比(C/D比)、急性移植排斥反应和病毒感染的影响。方法:采用相似免疫抑制治疗的肾移植受者(n=65)。扩增难解突变系统聚合酶链反应(ARMS-PCR)法扩增目标snp位点。结果:共纳入65例患者,男女比例为37/28。平均年龄38±1.75岁。CYP3A5*3、MDR-1 C3435T和PXR C25385T变异等位基因频率分别为95.38%、20.77%和26.92%。snp与他克莫司C/D比值无显著相关性。纯合子CYP3A5 *3/*3携带者在2周和8周时的C/D比有显著差异(P=0.015)。所研究的多态性与病毒感染和急性移植排斥反应无显著相关性(P>0.05)。结论:纯合子CYP3A5 *3/*3基因型影响他克莫司代谢率(C/D比)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran.

Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).

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来源期刊
Advanced pharmaceutical bulletin
Advanced pharmaceutical bulletin PHARMACOLOGY & PHARMACY-
CiteScore
6.80
自引率
2.80%
发文量
51
审稿时长
12 weeks
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