丹麦人群中iPLEX® ADME PGx Pro Panel及药物遗传学标记等位基因频率的评估。

Evaluation of the iPLEX® ADME PGx Pro Panel and allele frequencies of pharmacogenetic markers in Danes.

作者信息

Jensen Line, Børsting Claus, Dalhoff Kim, Morling Niels

机构信息

Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's Vej 11, 2100 Copenhagen, Denmark.

出版信息

Clin Biochem. 2016 Nov;49(16-17):1299-1301. doi: 10.1016/j.clinbiochem.2016.07.014. Epub 2016 Jul 25.

DOI:10.1016/j.clinbiochem.2016.07.014

PMID:27459874

Abstract

OBJECTIVES

The iPlex® ADME PGx Pro Panel was developed to investigate 191 polymorphisms including single nucleotide polymorphisms (SNPs), insertion-deletions (INDELS), and copy number variations (CNV) relevant for absorption, distribution, metabolism, and excretion (ADME) of drugs. The purpose of this study was to perform a technical evaluation of the iPlex® ADME PGx Pro Panel by genotyping 50 unrelated Danes and estimate preliminary genotype frequencies among Danes.

DESIGN AND METHODS

The investigations were performed by the use of PCR, single base extension (SBE) and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS).

RESULTS

The typing quality of 161 SNP assays was categorized as well performing or acceptable, whereas 22 SNP assays were categorized as either questionable or unacceptable. The frequencies of the genotypes observed in the Danish population were compared to those of the European reference population from the 1000 Genome Project. Three SNPs (rs737865, rs35167514, and rs34305973) showed statistically significantly differences between the frequencies of the 1000 Genomes Europeans and the Danes. The CNV assays could only be used as a guideline.

CONCLUSION

In conclusion, the iPlex® ADME PGx Pro Panel is a cost-effective way of genotyping genes relevant for ADME.

摘要

目的

开发iPlex® ADME PGx Pro Panel用于研究191种多态性，包括与药物吸收、分布、代谢和排泄（ADME）相关的单核苷酸多态性（SNP）、插入缺失（INDEL）和拷贝数变异（CNV）。本研究的目的是通过对50名不相关的丹麦人进行基因分型，对iPlex® ADME PGx Pro Panel进行技术评估，并估计丹麦人中的初步基因型频率。

设计与方法

采用聚合酶链反应（PCR）、单碱基延伸（SBE）和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）进行研究。

结果

161个SNP检测的分型质量被归类为表现良好或可接受，而22个SNP检测被归类为有问题或不可接受。将丹麦人群中观察到的基因型频率与1000基因组计划中的欧洲参考人群的频率进行比较。三个SNP（rs737865、rs35167514和rs34305973）在1000基因组欧洲人和丹麦人的频率之间显示出统计学上的显著差异。CNV检测只能作为一个指导。