CYP3A5 gene polymorphisms and their impact on dosage and trough concentration of tacrolimus among kidney transplant patients: a systematic review and meta-analysis.,The Pharmacogenomics Journal

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CYP3A5 gene polymorphisms and their impact on dosage and trough concentration of tacrolimus among kidney transplant patients: a systematic review and meta-analysis.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41397-019-0144-7
Abdul Rafay Khan ₁ , Ali Raza ₁ , Sadaf Firasat ₁ , Aiysha Abid ₁

Affiliation

Tacrolimus is an immunosuppressive drug widely used in kidney transplantation. Cytochrome P450 3A5 (CYP3A5) protein is involved in tacrolimus metabolism. Single nucleotide polymorphism in the CYP3A5 gene (6986A>G) results in alteration in metabolic activity of CYP3A5 protein which eventually affects the tacrolimus concentration. Patients with CYP3A5 expresser genotypes (A/A *1/*1 and A/G *1/*3) metabolize tacrolimus more rapidly than CYP3A5 nonexpressers (G/G *3/*3). We performed meta-analysis to estimate the effect of CYP3A5 polymorphism on the trough concentration-dose ratio (Co/D) and risk of renal allograft rejection with similar post-transplant periods and Asian vs. European populations. Our results showed that the tacrolimus Co/D ratio is significantly lower in CYP3A5 expresser group as compared with nonexpresser in Asian as well as in European populations at any post-transplant period (p < 0.00001). No significant association was found with renal allograft rejection episodes between expressers and nonexpressers in European populations (OR: 1.12; p = 0.47). Interestingly, Asian population (with expresser genotypes) and patients after 3 years post-transplantation (with expresser genotypes) have a higher risk of rejection (OR: 1.62; p < 0.05), (OR: 1.68; p < 0.05), respectively. This could be due to high prevalence of expresser genotypes in Asian population. Few tacrolimus-based studies are identified with long-term graft survival. There is a need to have more studies looking for long-term graft survival in expresser as well as no-expresser groups especially in Asian populations who have high frequency of CYP3A5 functional genotype.

中文翻译：

CYP3A5基因多态性及其对他克莫司剂量和谷浓度的影响在肾脏移植患者中：系统评价和荟萃分析。

他克莫司是一种广泛用于肾脏移植的免疫抑制药物。细胞色素P450 3A5（CYP3A5）蛋白参与他克莫司的代谢。CYP3A5基因的单核苷酸多态性（6986A> G）导致CYP3A5蛋白代谢活性的改变，最终影响他克莫司的浓度。具有CYP3A5表达基因型（A / A * 1 / * 1和A / G * 1 / * 3）的患者比CYP3A5非表达者（G / G * 3 / * 3）代谢他克莫司更快。我们进行了荟萃分析，以评估CYP3A5基因多态性对谷浓度-剂量比（Co / D）的影响以及移植后相似时期以及亚洲和欧洲人群肾移植排斥的风险。我们的结果表明，在任何移植后时期，CYP3A5表达组的他克莫司Co / D比在亚洲人群和欧洲人群中的CYP3A5表达组明显低于非表达组（p <0.00001）。在欧洲人群中，在表达者和非表达者之间没有发现同种异体肾移植排斥反应的显着相关性（OR：1.12； p = 0.47）。有趣的是，亚洲人群（具有表达基因型）和移植后3年后的患者（具有表达基因型）分别具有较高的排斥风险（OR：1.62； p <0.05），（OR：1.68； p <0.05）。这可能是由于亚洲人群中表达基因型的普遍性所致。很少有以他克莫司为基础的研究能够长期移植存活。

更新日期：2020-01-06

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