A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene.

IF 1.5 Q3 UROLOGY & NEPHROLOGY American journal of clinical and experimental urology Pub Date : 2023-01-01
Priyal M Chauhan, Rashmi J Hemani, Nilay D Solanki, Nitiraj B Shete, Sishir D Gang, Abhijit M Konnur, Ratika Srivastava, Sachchida Nand Pandey
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Abstract

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene CYP3A5 associated with Tacrolimus metabolism. Studies focusing on genetic variants in the CYP3A5 gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of CYP3A5 and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of CYP3A5 genotype (rs776746) with concentration/dose (Co/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the CYP3A5 on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus Co/D ratio is significantly lower in the CYP3A5 expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the CYP3A5 variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus Co/D have been found to be significantly linked to the patient's CYP3A5 genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the CYP3A5 genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.

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一项系统综述和荟萃分析表明,他克莫司治疗肾移植患者的疗效与CYP3A5基因的遗传变异有关。
他克莫司是一种免疫抑制剂,具有狭窄的治疗指数和药代动力学变异性。这种变异性可能归因于与他克莫司代谢相关的基因CYP3A5的遗传变异。CYP3A5基因变异与他克莫司代谢相关的研究已经发表,对这些已发表的文章进行荟萃分析,可能为今后肾移植患者的研究和临床管理提供方向。在本系统综述和荟萃分析中,我们回顾和分析了PubMed数据库和临床试验(www.clinicaltrials.gov)中为确定CYP3A5遗传变异与他克莫司代谢之间的关系而进行的研究和临床试验。该荟萃分析还评估了肾移植患者CYP3A5基因型(rs776746)与他克莫司浓度/剂量(Co/D)的相关性。本系统回顾了59篇已发表的关于CYP3A5与他克莫司剂量遗传关系的文章。荟萃分析显示,在移植后的任何时期,CYP3A5表达组的他克莫司Co/D比在亚洲、欧洲以及混合人群中均显著低于非表达组(PCYP3A5变异(rs776746)与他克莫司剂量的确定有临床相关性)。他克莫司Co/D的变异已被发现与患者的CYP3A5遗传变异(rs776746)显著相关。他克莫司药代动力学中涉及的其他遗传变异的加入可能决定药物剂量的有效方案。我们的荟萃分析证实,CYP3A5遗传变异(rs776746)分析与肾移植患者个体化他克莫司剂量确定相关。
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