CYP3A5 基因多态性与肾移植：实现个体化免疫抑制的关键。

CYP3A5 Polymorphism in Renal Transplantation: A Key to Personalized Immunosuppression.

机构信息

Department of Nephrology, Saraswati Kidney Care Center, Nagpur, Maharashtra, India; Department of Nephrology, Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, India.

出版信息

Transplant Proc. 2023 Jun;55(5):1305-1309. doi: 10.1016/j.transproceed.2023.02.043. Epub 2023 Mar 25.

DOI:10.1016/j.transproceed.2023.02.043

PMID:36973144

Abstract

BACKGROUND

Tacrolimus is essential for the maintenance of immunosuppression after a kidney transplant. CYP3A5 is the gene that metabolizes tacrolimus, and polymorphism in this gene affects the metabolizing status.

AIM

To assess the genetic polymorphism status of patients undergoing kidney transplantation and determine its impact on graft function and complications in the post-transplant period.

METHODS

We retrospectively included the patients who had undergone a kidney transplant and had positive genetic polymorphism of the CYP3A5 gene. Based on loss of alleles, patients were categorized as non-expresser (loss of both alleles), intermediate expresser (loss of one allele), and expresser (no loss of allele) denoted by CYP3A5*3/3, CYP3A51/3, and CYP3A51/*1, respectively. Data were analyzed with descriptive statistics.

RESULTS

Of 25 patients, 60%, 32%, and 8% were non-expressers, intermediate-expressers, and expressers, respectively. The mean tacrolimus trough concentration to dose ratio after 6 months of the transplant was higher in non-expressers than intermediate-expressers and expressers (213 vs 85 and 46 ng/mL/mg/kg/d, respectively). The graft function was normal in all 3 groups except for graft rejection 1 patient in the expresser group. Compared with expressers, urinary tract infections (42.9% and 62.5%) and new-onset diabetes after transplantation (28.6% and 12.5%) were more frequent in non-expresser and intermediate expressers, respectively. The proportion of patients developing new-onset diabetes after transplantation was lower with the pre-transplant diagnosis of CYP3A5 polymorphism (16.7% vs 23.1%).

CONCLUSION

Genotype-based dosing of tacrolimus helps achieve the desired therapeutic concentrations that can help to optimize graft outcomes and reduce the tacrolimus-related adverse effects. Pre-transplant evaluation of CYP3A5 can be more helpful in planning treatment strategies for optimized outcomes after kidney transplantation.

摘要

背景

他克莫司是肾移植后维持免疫抑制所必需的。CYP3A5 是代谢他克莫司的基因，该基因的多态性影响代谢状态。

目的

评估接受肾移植患者的基因多态性状态及其对移植后移植物功能和并发症的影响。

方法

我们回顾性纳入了接受肾移植且 CYP3A5 基因存在阳性遗传多态性的患者。根据等位基因缺失情况，患者分为非表达者（两个等位基因缺失）、中间表达者（缺失一个等位基因）和表达者（无等位基因缺失），分别表示为 CYP3A5*3/3、CYP3A51/3 和 CYP3A51/*1。采用描述性统计分析数据。

结果

25 例患者中，非表达者、中间表达者和表达者分别占 60%、32%和 8%。移植后 6 个月时，非表达者的他克莫司谷浓度与剂量比值高于中间表达者和表达者（分别为 213、85 和 46ng/mL/mg/kg/d）。除表达者组 1 例发生移植物排斥外，3 组患者的移植物功能均正常。与表达者相比，非表达者和中间表达者的尿路感染（42.9%和 62.5%）和新发移植后糖尿病（28.6%和 12.5%）更为常见。具有 CYP3A5 多态性的患者发生新发移植后糖尿病的比例较低（16.7%比 23.1%）。