The genetic landscape of major drug metabolizing cytochrome P450 genes—an updated analysis of population-scale sequencing data

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2022-09-06 DOI:10.1038/s41397-022-00288-2

Yitian Zhou, Volker M. Lauschke

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引用次数: 15

Abstract

Genes encoding cytochrome P450 enzymes (CYPs) are extremely polymorphic and multiple CYP variants constitute clinically relevant biomarkers for the guidance of drug selection and dosing. We previously reported the distribution of the most relevant CYP alleles using population-scale sequencing data. Here, we update these findings by making use of the increasing wealth of data, incorporating whole exome and whole genome sequencing data from 141,614 unrelated individuals across 12 human populations. We furthermore extend our previous studies by systematically considering also uncharacterized rare alleles and reveal that they contribute between 1.5% and 17.5% to the overall genetically encoded functional variability. By using established guidelines, we aggregate and translate the available sequencing data into population-specific patterns of metabolizer phenotypes. Combined, the presented data refine the worldwide landscape of ethnogeographic variability in CYP genes and aspire to provide a relevant resource for the optimization of population-specific genotyping strategies and precision public health.

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主要药物代谢细胞色素 P450 基因的遗传格局--对群体规模测序数据的最新分析

编码细胞色素 P450 酶（CYPs）的基因具有极高的多态性，多种 CYP 变异构成了指导药物选择和剂量的临床相关生物标志物。我们曾利用人群规模的测序数据报告了最相关的 CYP 等位基因的分布情况。在这里，我们利用日益丰富的数据更新了这些发现，纳入了来自 12 个人类群体中 141,614 个无关联个体的全外显子组和全基因组测序数据。此外，我们还系统地考虑了未表征的罕见等位基因，从而进一步扩展了之前的研究，并发现这些等位基因对整体基因编码功能变异的贡献率在 1.5% 到 17.5% 之间。通过使用既定指南，我们汇总了现有测序数据，并将其转化为特定人群的代谢物表型模式。综合上述数据，我们完善了全球范围内 CYP 基因的人种地理变异情况，并希望为优化特定人群基因分型策略和精准公共卫生提供相关资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.