The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305386 | PMC |
| http://dx.doi.org/10.1038/s41598-018-36085-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-Nucleotide Polymorphisms Associated with Mercury Levels and Neurological Symptoms: An Overview.
Toxics
March 2024
Program of Post-Graduation in Public Health and Environment, National School of Public Health (ENSP), Oswald Cruz Foundation (Fiocruz), Rio de Janeiro 21041-210, Brazil.
Mercury (Hg) pollution is a global public health concern because of its adverse effects on the environment and health. Single-nucleotide polymorphisms (SNPs) have been associated with Hg levels and outcomes. The aim of this review was to describe the research and discuss the evidence on the genetic susceptibility of Hg-exposed individuals to the development of neurocognitive disorders.
View Article and Find Full Text PDFAllele and genotype frequencies of CYP3A4, CYP3A5, CYP3A7, and GSTP1 gene polymorphisms among mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations.
Clin Exp Pharmacol Physiol
February 2022
Department of Pharmacology, Basic Medical School, Peking University, Beijing, China.
Over 50% prescribed drugs are metabolised by cytochrome P450 3A (CYP3A) and glutathione S-transferase pi (GSTP1) adds a glutathione to the oxidative products by CYP3A, which increases the hydrophilic property of metabolites and facilitates the excretion. Single nucleotide polymorphisms (SNPs) of CYP3A and GSTP1 show a diverse allele and genotype frequencies distribution among the world populations. The present study aimed to investigate the genotype and allele frequency distribution patterns of CYP3A4, CYP3A5, CYP3A7 and GSTP1 polymorphisms among healthy participants in mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations.
View Article and Find Full Text PDFCYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation.
Gene
January 2022
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China. Electronic address:
Aim: The purpose of this study was to investigate the effect of CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in liver transplant recipients and donors on tacrolimus concentrations in the early stages after liver transplantation.
Methods: One hundred and thirty-eight liver transplant recipients and matched donors were genotyped for CYP3A7 (rs10211 and rs2257401), CYP3A4 (rs4646437 and rs2242480), and CYP3A5*3 (rs776746) polymorphisms. The relationships between dose-adjusted trough concentrations (C/D) of tacrolimus and corresponding genotypes were investigated.
CYP3A Polymorphism and Chronic Mercury Intoxication.
Bull Exp Biol Med
February 2020
East-Siberian Institute of Medical and Ecological Research, Angarsk, Russia.
We analyzed the relationship between polymorphic loci of CYP3A genes (CYP3A4 (rs2740574), CYP3A5 (rs776746) and CYP3A7 (rs2257401)) with the development of chronic mercury intoxication. Of 170 men examined, 120 were workers chronically exposed to mercury vapors and 50 were carriers of GG-HSPA1B (+1267A/G) genotype associated with chronic mercury intoxication. Urinary content of 4-hydroxyantipyrine (4-HAP) generated in the reaction predominantly catalyzed by CYP3A4/CYP3A5 was studied in workers without chronic mercury intoxication (group 1, N=46) and patients in the delayed period of chronic mercury intoxication (group 2, N=74) depending on the genotypes of CYP3A4 and CYP3A5.
View Article and Find Full Text PDFCYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria.
Eur J Clin Pharmacol
November 2019
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China.
Purpose: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria.
Methods: Genetic variants including CYP3A5*3 (rs776746), CYP3A4*1G (rs2242480), rs4646437, and CYP3A7 rs2257401 and rs10211 were detected in 70 pediatric patients with nephrotic range proteinuria. The relationships of dose-adjusted trough concentration (C) of tacrolimus with corresponding genotypes were investigated.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!