Summary of Biology Doctoral Thesis: Study on polymorphisms mutations of CYP2C9, CYP2C19, CYP3A5 and CYP2D6 cytochrome P450 in Kinh Vietnamese

Study on Polymorphisms/Mutations of CYP2C9, CYP2C19, CYP3A5 and CYP2D6 Cytochrome P450 in Kinh Vietnamese

Author: Vu Phuong Nhung

Major: Biotechnology

Field: Graduate University of Science and Technology

Document Content:

This doctoral thesis investigates the genetic variations, specifically polymorphisms and mutations, within the CYP2C9, CYP2C19, CYP3A5, and CYP2D6 cytochrome P450 genes in the Kinh Vietnamese population. Cytochrome P450 enzymes play a crucial role in drug metabolism, and variations in these genes can significantly impact how individuals respond to medications, leading to differences in drug efficacy and the risk of adverse drug reactions (ADRs). Despite the established importance of pharmacogenetics in personalized medicine, understanding of genetic diversity in these key drug-metabolizing genes within the Vietnamese population has been limited. This study aims to address this gap by establishing a genetic variant database, identifying genotype and allele frequencies, and performing in silico functional analysis of novel variants. The research utilizes molecular biology techniques, including Sanger sequencing and MLPA, to analyze DNA samples from Kinh Vietnamese volunteers. The findings are expected to provide valuable scientific information contributing to the advancement of pharmacogenetics and personalized medicine in Vietnam.

Detailed Table of Contents:

• INTRODUCTION
• 1. The necessity of research
• 2. Research objective
• 3. Research content
• CHAPTER 1. LITERATURE OVERVIEW
• 1.1. Cytochrome P450 (CYP450) and drug metabolism in liver
• 1.2. Genetic polymorphism of genes encoding for CYP450 enzyme involved in drug metabolism
• 1.3. Effect of pharmacogenes variations on ADRs and variable drug responses
• 1.4. Methodologies applied in study of CYP450 genetic variations
• 1.5. Study on genetic variation of CYP450 in Vietnamese and research scope
• CHAPTER 2. MATERIALS AND METHODS
• 2.1. Study subjects
• 2.2. Instruments and equipment
• 2.3. Methodologies
• 2.3.1. Total DNA extraction
• 2.3.2. DNA quantification
• 2.3.3. Amplification of CYP2C9, CYP2C19, CYP2D6 and CYP3A5
• 2.3.4. Sanger sequencing
• 2.3.5. MLPA
• 2.3.6. Longrange (LR) PCR
• 2.3.7. Real-time PCR
• 2.3.8. Data analysis
• 2.3.9. Functional prediction of novel variants
• CHAPTER 3. RESULTS AND DISCUSSION
• 3.1. Total DNA extraction
• 3.2. Amplification of CYP2C9, CYP2C19, CYP2D6, CYP3A5 and sequencing
• 3.3. Genetic variations of CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in Kinh
• 3.3.1. Genetic variants of CYP2C9
• 3.3.2. Genetic variants of CYP2C19
• 3.3.3. Genetic variants of CYP2D6