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京族越南人中细胞色素基因的拷贝数变异

Copy number variations of cytochrome genes in Kinh Vietnamese.

作者信息

Vu Nhung Phuong, Nguyen Ton Dang, Nguyen Binh Huy, Nguyen Duong Thuy, Nong Hai Van, Nguyen Ha Hai

机构信息

Department of Biotechnology, Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam.

Genome Analysis Laboratory, Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi 100000, Vietnam.

出版信息

Asian Biomed (Res Rev News). 2023 Sep 17;17(2):84-92. doi: 10.2478/abm-2023-0048. eCollection 2023 Apr.

Abstract

BACKGROUND

The cytochrome P450 () family is well known as a major group of drug metabolizing enzymes. The polymorphism of genes is the main factor having an impact on the interindividual difference in drug response, including drug efficacy and drug safety. The single nucleotide polymorphism (SNPs) of Vietnamese Kinh has been widely studied, but information about the copy number variations (CNVs) of other genes is still unknown.

OBJECTIVE

To identify the CNV variability of in 154 healthy unrelated Kinh Vietnamese, except e, which was previously reported.

METHODS

Multiplex Ligation-Dependent Probe Amplification (MLPA) was applied for determination of copy number of 10 genes. Later, PCR or quantitative PCR (qPCR) was used to confirm the detected CNVs in randomly chosen subjects.

RESULTS

Of the 154 subjects, along with , 4 other genes showed CNVs including duplications (), deletions ( and ), and both duplications and deletions (). Among these, exhibited the greatest frequency of CNVs compared with other , in which Del accounted for 11%. Meanwhile, allele Del showed the lowest frequency with only 0.3%.

CONCLUSIONS

The present study provides new insight into CNVs in the Kinh Vietnamese cohort. Our data have contributed to genetic profiling of CNVs in Vietnam, which would be helpful for facilitating implementation of pharmacogenetics in drug dosing adjustment in Vietnam.

摘要

背景

细胞色素P450(CYP)家族是众所周知的主要药物代谢酶类。CYP基因多态性是影响药物反应个体差异(包括药物疗效和药物安全性)的主要因素。越南京族的细胞色素P450基因单核苷酸多态性(SNPs)已得到广泛研究,但其他CYP基因的拷贝数变异(CNVs)信息仍不明确。

目的

除先前报道的CYP2E1外,鉴定154名健康无亲缘关系的越南京族个体中CYP基因的CNV变异性。

方法

采用多重连接依赖探针扩增技术(MLPA)测定10个CYP基因的拷贝数。随后,使用聚合酶链反应(PCR)或定量聚合酶链反应(qPCR)对随机选择的受试者中检测到的CNVs进行确认。

结果

在154名受试者中,除CYP2E1外,其他4个CYP基因也存在CNVs,包括重复(CYP2D6)、缺失(CYP2C19和CYP2C9)以及重复和缺失同时存在(CYP3A4)。其中,CYP2C9的CNV频率与其他CYP基因相比最高,其中缺失型(Del)占11%。同时,Del等位基因频率最低,仅为0.3%。

结论

本研究为越南京族人群的CYP基因CNVs提供了新的见解。我们的数据有助于越南CYP基因CNVs的遗传图谱绘制,这将有助于促进越南药物剂量调整中药理学的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba19/10505059/998a6c4e679f/j_abm-2023-0048_fig_001.jpg

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