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分析 ABCB1 基因多态性及其对肾移植受者他克莫司血药浓度的影响。

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients.

机构信息

Department of Immunology and Transplant Immunology, "Carol Davila" University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania.

Department of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, 022328 Bucharest, Romania.

出版信息

Int J Mol Sci. 2024 Oct 12;25(20):10999. doi: 10.3390/ijms252010999.

Abstract

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate () correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.

摘要

他克莫司(Tc)是一种用于移植患者的免疫抑制剂,但它的治疗范围很窄,因此精确的剂量至关重要。本研究调查了三个单核苷酸多态性(SNPs)(ABCB1 3435C>T、1236C>T、2677G>T/A)与 Tc 水平随时间的关系,以更好地了解它们在个性化医学中的作用。我们在四个不同的时期进行了研究:移植后 1-14 天、15-30 天、31-60 天和 60 天以上。该分析包括关于 Tc 血液水平的三个 SNPs 的等位基因、基因型、单倍型和二倍型频率。确定了统计学意义,并在适当的情况下应用了错误发现率(FDR)校正。在 C(ABCB1 C1236T)、A 等位基因(ABCB1 G2677T/A)、CAC 单倍型和较低的 Tc 水平之间发现了显著的关联。CAC-TGT 和 TGT-TGT 二倍型显著影响患者对药物的代谢方式。TGT 单倍型和 AA 基因型(ABCB1 G2677T/A)与较高的 Tc 水平相关,表明存在长期的遗传影响。遗传因素,特别是某些 SNPs 和二倍型,显著影响 Tc 血液水平,其影响随时间而变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78b1/11507373/978a32cf4695/ijms-25-10999-g001.jpg

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