在加纳一家三级医院的肾衰竭患者人群中，对已知影响他克莫司每剂量血药谷浓度的单核苷酸多态性进行描述性研究。

A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana.

机构信息

Department of Medicine, University of Ghana Medical School, Legon, Ghana.

Center for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, University of Ghana, P.O. Box GP 4236, Legon, Accra, Ghana.

出版信息

BMC Res Notes. 2024 Jul 29;17(1):210. doi: 10.1186/s13104-024-06868-8.

DOI:10.1186/s13104-024-06868-8

PMID:39080672

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11288130/

Abstract

BACKGROUND

The burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required.

OBJECTIVE

This study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure.

METHOD

This cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).

RESULTS

Participants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A51/3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A53/3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A41B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype.

CONCLUSION

SNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.

摘要

背景

加纳慢性肾脏病（CKD）和肾衰竭的负担呈上升趋势，CKD 的患病率估计为 13.3%。进展为肾衰竭的 CKD 患者需要维持生命的肾脏替代治疗（KRT），而 KRT 在加纳几乎仅作为血液透析提供。由于其相对成本效益以及在生存和生活质量方面的优势，对于因肾衰竭而无法逆转的患者来说，肾移植被认为是最佳的 KRT 选择。然而，由于移植可能引发潜在的器官排斥反应，因此需要使用免疫抑制剂，如他克莫司剂量。

目的

本研究旨在确定 CYP3A5、CYP3A4 和 MDR1 基因中的单核苷酸多态性，这些基因影响加纳肾衰竭患者中他克莫司的药代动力学。

方法

这项横断面研究包括 82 名在科勒-布教学医院（KBTH）肾脏和透析科接受维持性血液透析的肾衰竭患者。收集了临床和人口统计学数据并分离了基因组 DNA。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对特定 SNP 进行了样本基因分型。

结果

82 名参与者中，58/82（70.73%）携带野生型 CYP3A5*1/1 AA 基因型，20/82（24.39%）携带杂合型 CYP3A51/3 AG 基因型，4/82（4.88%）携带纯合型突变 CYP3A53/3 GG 基因型。此外，6/82（7.32%）携带野生型 AA 基因型，11/82（13.41%）携带杂合型 AG 基因型，65/82（79.27%）携带 CYP3A41B（-290 A>G）的纯合型突变 GG 基因型。对于 MDR1_Ex21（2677 G>T），81/82（98.78%）携带野生型 GG 基因型，而 1/82（1.22%）携带杂合型 GT 基因型。对于 MDR1_Ex26（3435 C>T），63/82（76.83%）携带野生型 CC 基因型，18/82（21.95%）携带杂合型 CT 基因型，而 1/82（1.22%）携带突变型 TT 基因型。