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精神科医疗中的药物基因组学洞察:揭示 15000 名患者中的新型可操作性、等位基因特异性 CYP2D6 拷贝数变异和表型转化。

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients.

机构信息

Department of Cancer Pharmacology & Pharmacogenomics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.

Tempus AI, Inc., Chicago, IL, USA.

出版信息

Mol Psychiatry. 2024 Nov;29(11):3495-3502. doi: 10.1038/s41380-024-02588-4. Epub 2024 May 23.


DOI:10.1038/s41380-024-02588-4
PMID:38783055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11541190/
Abstract

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

摘要

药物基因组学检测已成为精神科医生临床决策的辅助手段,但仍需要更多数据来评估其在临床实践中的效用及其对患者护理的潜在影响。在这项横断面研究中,我们确定了在接受精神科护理的患者中药物基因组学可操作性的真实世界流行率。潜在的可操作性是基于 CYP2C19 和 CYP2D6 表型的流行率,包括 CYP2D6 等位基因特异性拷贝数变异 (CNV)。在有可用药物数据的患者中,联合可操作性还纳入了 CYP2D6 表型转化和新型 CYP2C-TG 单倍型。在接受临床药物基因组学检测的 15000 名患者中,65%的患者具有潜在可操作的 CYP2D6 和 CYP2C19 表型,2%的所有患者的表型分配受到 CYP2D6 等位基因特异性 CNV 的影响。在 4114 名有药物数据的患者中,42%的患者因药物相互作用发生 CYP2D6 表型转化,20%的患者携带可能改变可操作性的新型 CYP2C 单倍型。共有 87%的患者存在某种形式的潜在可操作性,包括遗传发现和/或表型转化。通过下一代测序检测到的遗传变异导致总体 22%的个体的表型重新分配(CYP2D6 为 2%,CYP2C19 为 20%)。总体而言,使用下一代测序的药物基因组学检测确定了大多数接受精神科护理的患者具有潜在可操作性。早期药物基因组学检测可能为临床医生提供有针对性的见解,以帮助他们进行药物处方,从而优化精神科护理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/1a84b7719697/41380_2024_2588_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/cd909f93aec8/41380_2024_2588_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/b153f405cce2/41380_2024_2588_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/1a84b7719697/41380_2024_2588_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/cd909f93aec8/41380_2024_2588_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/b153f405cce2/41380_2024_2588_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76fe/11541190/1a84b7719697/41380_2024_2588_Fig3_HTML.jpg

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Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes.

Hum Genomics. 2025-5-28

本文引用的文献

[1]
Imputation of race and ethnicity categories using genetic ancestry from real-world genomic testing data.

Pac Symp Biocomput. 2024

[2]
Response to "What is the Current Clinical Impact of the CYP2C:TG Haplotype?".

Clin Pharmacol Ther. 2024-2

[3]
The Use of Next-Generation Sequencing in Pharmacogenomics.

Clin Lab. 2023-8-1

[4]
Impact of CYP2C:TG Haplotype on CYP2C19 Substrates Clearance In Vivo, Protein Content, and In Vitro Activity.

Clin Pharmacol Ther. 2023-11

[5]
The role of phenoconversion in the pharmacogenetics of psychiatric medication.

Pharmacogenomics. 2023-6

[6]
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.

Clin Pharmacol Ther. 2023-7

[7]
Psychiatry pharmacogenomics: Africans are not at the table.

Lancet Psychiatry. 2023-2

[8]
CYP2D6 pharmacogenetics and phenoconversion in personalized medicine.

Expert Opin Drug Metab Toxicol. 2022-11

[9]
Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.

Neurosci Biobehav Rev. 2023-1

[10]
Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta-Analysis of Prospective, Controlled Clinical Trials.

Clin Pharmacol Ther. 2022-12

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