利用次世代定序技術建立藥物基因體學之基因檢測平台

Establishment of pharmacogenomics testing platform based on next-generation sequencing

劉昱希(Yu-Shi Liu)

指導教授 ： 陳沛隆

國立臺灣大學/醫學院/基因體暨蛋白體醫學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201703406

摘要

無資料

關鍵字

藥物基因體學 ； 藥物動力學／藥效學 ； 個人化醫療 ； 次世代定序 ； 臺灣人體生物資料庫

並列摘要

Medical drugs show different efficacy and/or adverse drug reactions (ADRs) on patients. This is mostly due to the variations of DNA sequence. Pharmacogenomics is the study and applications about how genetic variations in individuals influence the drug response, which is composed of both pharmacokinetics and pharmacodynamics. Pharmacogenomics plays an important role in optimal drug choice and drug dosing. There are numerous genes involved in pharmacogenomics, which imposes a big challenge because of the complexity and high cost using conventional techniques like Sanger sequencing. In the present study, we set up a genetic testing platform through capture-based target enrichment followed by next-generation sequencing (NGS). Our panel covered approximately 345 major pharmacogenomics genes, including pharmacokinetics genes (for example, ADME genes regarding to absorption, distribution, metabolism and excretion) and pharmacodynamics genes, such as ABCB1, CFTR, CYPs, DRYP, EGFR, HLAs, KRAS, NAT2, RYR1, TPMT, UGT1A1 and VKORC1. A great proportion of our genes overlapped with those listed on FDA labeled biomarkers, Pharmacogenomics Knowledgebase (PharmGKB) and PharmaADME. We applied this panel to 34 individuals, including 6 controls with whole genome sequencing data from Taiwan Biobank for technical validation and 28 patients recruited from NTUH, trying to find specific ADR gene biomarkers. Also, we used LOVD (Leiden Open Variation Database) system to build a pharmacogenomics database in a uniform table format contains information on gene, variant, and drug response according to the PharmGKB clinical annotation file of warfarin, dabigatran, rivaroxaban, oxaliplatin and paclitaxel. In conclusion, the NGS-based pharmacogenomics panel and the pharmacogenomics LOVD database could be beneficial for precision medicine in clinical applications and academic research.

並列關鍵字

Pharmacogenomics ； PK/PD ； precision medicine ； Next-generation sequencing (NGS) ； Leiden Open Variation Database (LOVD) ； Taiwan Biobank

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