Handbook of Pharmacogenomics and Stratified Medicine - 1st Edition - ISBN: 9780123868824, 9780123868831

Handbook of Pharmacogenomics and Stratified Medicine

1st Edition

Editor-in-Chiefs: Sandosh Padmanabhan
eBook ISBN: 9780123868831
Hardcover ISBN: 9780123868824
Imprint: Academic Press
Published Date: 6th May 2014
Page Count: 1118
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Description

Handbook of Pharmacogenomics and Stratified Medicine is a comprehensive resource to understand this rapidly advancing field aiming to deliver the right drug at the right dose to the right patient at the right time. It is designed to provide a detailed, but accessible review of the entire field from basic principles to applications in various diseases. The chapters are written by international experts to allow readers from a wide variety of backgrounds, clinical and non-clinical (basic geneticists, pharmacologists, clinicians, trialists, industry personnel, ethicists) to understand the principles underpinning the progress in this area, the successes, failures and the challenges ahead. To be accessible to the widest range of readers, the clinical application section introduces the disease process, existing therapies, followed by  pharmacogenomics and stratified medicine details.

Medicine is the cornerstone of modern therapeutics prescribed on the basis that its benefit should outweigh its risk. It is well known that people respond differently to medications and in many cases the risk-benefit ratio for a particular drug may be a gray area. The last decade has seen a revolution in genomics both in terms of technological innovation and discovering genetic markers associated with disease. In parallel there has been steady progress in trying to make medicines safer and tailored to the individual. This has occurred across the whole spectrum of medicine, some more than others. In addition there is burgeoning interest from the pharmaceutical industry to leverage pharmacogenomics for more effective and efficient clinical drug development.

Key Features

  • Provides clinical and non-clinical researchers with practical information normally beyond their usual areas of research or expertise
  • Includes an basic principles section explaining concepts of basic genetics, genetic epidemiology, bioinformatics,  pharmacokinetics and pharmacodynamics
  • Covers newer technologies– next generation sequencing, proteomics, metabolomics
  • Provides information on animal models, lymphoblastoid cell lines, stem cells
  • Provides detailed chapters on a wide range of disease conditions, implementation and regulatory issues
  • Includes chapters on the global implications of pharmacogenomics

Readership

Clinical researchers across medical disciplines, genetics, molecular biology, molecular diagnostics, and genomic studies who are working on the various aspects of translational genetics and genomics; pharmacologists working with clinicians on these studies

Table of Contents

  • Dedication
  • Foreword
  • Preface
  • Acknowledgments
  • Part 1: Introduction
    • Chapter 1. Pharmacogenomics and Stratified Medicine
      • Abstract
      • 1.1 Overview
      • 1.2 The Genetic Basis of Drug Response and Adverse Effects
      • 1.3 Single-Gene Studies
      • 1.4 Genome-Wide Association Studies in Pharmacogenomics
      • 1.5 The Road to Personalization and Stratification
      • 1.6 Pharmacogenetic Biomarkers and Companion Diagnostics
      • 1.7 Economic Challenges
      • 1.8 Conclusions
      • References
  • Part 2: Basic Genetics
    • Chapter 2. Basic Genetics: The Cell, Mitosis and Meiosis, and Mendelian Laws
      • Abstract
      • Acknowledgments
      • 2.1 Overview of the Cell: Anatomy, Components, and Function
      • 2.2 Cell Reproduction: Cell Cycle and Mitosis
      • 2.3 Meiosis
      • 2.4 Mendelian Laws
      • 2.5 Public Databases for Biomedical Research in Humans
      • 2.6 Conclusion
      • Glossary
      • References
    • Chapter 3. The Human Genome, Gene Regulation, and Genomic Variation
      • Abstract
      • 3.1 Overview: Structure of the Human Genome
      • 3.2 Gene Structures
      • 3.3 Gene Expression
      • 3.4 Gene Regulation
      • 3.5 Genomic Variation
      • 3.6 Conclusion
      • References
    • Chapter 4. Epigenetics
      • Abstract
      • 4.1 Overview
      • 4.2 DNA Methylation
      • 4.3 Histones and Variants
      • 4.4 Epigenetic Disorders And Therapies
      • 4.5 Conclusion
      • References
  • Part 3: Experimental and Discovery Platforms
    • Chapter 5. Animal Models in Pharmacogenomics
      • Abstract
      • 5.1 Overview
      • 5.2 Rodent Models
      • 5.3 Nonrodent Models of Human Disease
      • 5.4 Genetic/Genomic Resources
      • 5.5 Ethical Issues of Animal Experimentation
      • 5.6 Caution and Limitations
      • 5.7 Applications of in Vivo Models in Pharmacogenomic Research
      • 5.8 Rodent Models in Pharmacogenomics
      • 5.9 Conclusion
      • References
    • Chapter 6. Human Lymphoblastoid Cell Lines in Pharmacogenomics
      • Abstract
      • Acknowledgments
      • 6.1 Overview
      • 6.2 Generation of LCLs
      • 6.3 Biological Characteristics of LCLs
      • 6.4 Potentials and Limitations of LCL Applications
      • 6.5 Future Perspectives
      • References
    • Chapter 7. Liver Expression Quantitative Trait Loci (eQTL) and Related Approaches in Pharmacogenomic Studies
      • Abstract
      • Acknowledgments
      • 7.1 Overview
      • 7.2 Liver eQTL Studies
      • 7.3 Future Directions
      • 7.4 Conclusion
      • Glossary
      • Acronyms and Abbreviations
      • References
    • Chapter 8. Next-Generation Sequencing
      • Abstract
      • 8.1 Overview
      • 8.2 First-Generation Sequencing: Chain Termination Method
      • 8.3 The Concept of Next-Generation Sequencing
      • 8.4 Application-Independent Data Analysis
      • 8.5 Genomic Applications
      • 8.6 Transcriptomic Applications
      • 8.7 Epigenomic Applications
      • 8.8 Metagenomic Applications
      • 8.9 Conclusions
      • References
    • Chapter 9. Proteomics
      • Abstract
      • 9.1 Overview
      • 9.2 Data Acquisition
      • 9.3 Data Analysis
      • 9.4 Discovery and Validation
      • 9.5 Personalized Medicine
      • 9.6 Conclusions
      • Acronyms
      • References
    • Chapter 10. Metabolomics
      • Abstract
      • 10.1 Overview
      • 10.2 Metabolomics techniques and technologies
      • 10.3 Analytical platform
      • 10.4 Analysis of metabolomic data
      • 10.5 Conclusion
      • References
    • Chapter 11. Stem Cells
      • Abstract
      • 11.1 Overview
      • 11.2 Stem Cell Types
      • 11.3 Stem Cell Culture Methods
      • 11.4 Molecular Signatures of Stem Cells
      • 11.5 Epigenomics of Stem Cells
      • 11.6 Pharmacogenomics of Stem Cells
      • 11.7 Potential of Stem Cells
      • 11.8 Future Prospects
      • Abbreviations
      • References
  • Part 4: Statistics, Bioinformatics and Databases
    • Chapter 12. Fundamentals of Complex Trait Genetics and Association Studies
      • Abstract
      • 12.1 Overview
      • 12.2 The Phenotype
      • 12.3 Population Genetics
      • 12.4 Association Studies
      • 12.5 Conclusions
      • References
    • Chapter 13. Bioinformatics: Concepts, Methods, and Data
      • Abstract
      • 13.1 Overview
      • 13.2 Analysis of Sequences of Nucleic Acids and Proteins
      • 13.3 Molecular Evolution and Phylogenetics
      • 13.4 Molecular Graphics and Protein Modeling
      • 13.5 Bioinformatics Databases
      • Glossary
      • References
    • Chapter 14. PharmGKB: The Pharmacogenomics Knowledgebase
      • Abstract
      • Acknowledgments
      • 14.1 Overview
      • 14.2 The PharmGKB Website
      • 14.3 Variant Annotations
      • 14.4 Clinical Annotations
      • 14.5 VIPs and Pathways
      • 14.6 Clinical Implementation: Consortia, CPIC, and Dosing Guidelines
      • 14.7 Projects in Development
      • 14.8 Conclusion
      • Glossary
      • Acronyms and Abbreviations
      • References
  • Part 5: Clinical Trials
    • Chapter 15. Clinical Trials in Pharmacogenomics and Stratified Medicine
      • Abstract
      • 15.1 Overview
      • 15.2 Phase I Studies
      • 15.3 Phase II Studies
      • 15.4 Phase III Studies
      • 15.5 Phase IV Trials
      • 15.6 Retrospective Analysis of Clinical Datasets
      • References
  • Part 6: Fundamental Pharmacogenomics
    • Chapter 16. CYP450 and Ethnicity
      • Abstract
      • 16.1 Overview
      • 16.2 Variation: Importance of Race/Ethnicity
      • 16.3 Variation: CYP450 Phenotyping
      • 16.4 CYP450 Variation in Different Racial/Ethnic Populations—CYP450 Families
      • 16.5 Future Perspectives
      • References
    • Chapter 17. Pharmacokinetic Pharmacogenomics
      • Abstract
      • 17.1 Overview
      • 17.2 Principles of Pharmacokinetics
      • 17.3 Adme: Pharmacogenomics
      • 17.4 Conclusions
      • References
    • Chapter 18. Pharmacodynamic Pharmacogenomics
      • Abstract
      • 18.1 Overview
      • 18.2 Basic Pharmacodynamics
      • 18.3 Pharmacodynamic Pharmacogenetics
      • 18.4 Conclusion: Pharmacodynamic Pharmacogenomics into Clinical Practice
      • Glossary
      • Acronyms and Abbreviations
      • References
    • Chapter 19. MicroRNA: Regulation of P450 and Pharmacogenetics
      • Abstract
      • 19.1 Overview
      • 19.2 miRNA Biogenesis
      • 19.3 miRNA Function
      • 19.4 miRNA Target Identification
      • 19.5 Regulation of Drug-Metabolizing P450s
      • 19.6 Regulation of Cancer-Related P450s
      • 19.7 Modulation of mirna Expression and its Toxicological Outcome
      • 19.8 miRNA Pharmacogenetics Associated with Disease or Drug Response
      • 19.9 miRNAs as Biomarkers and Therapeutic Targets
      • 19.10 miRNAs and Drug Response
      • 19.11 Conclusions
      • Glossary
      • Abbreviations
      • References
  • Part 7: Application in Therapeutics
    • Chapter 20. Adverse Drug Reactions
      • Abstract
      • 20.1 Overview
      • 20.2 Phase I Metabolism
      • 20.3 Phase II Metabolism
      • 20.4 Type B Adverse Drug Reactions
      • 20.5 Conclusion
      • Abbreviations and Acronyms
      • References
    • Chapter 21. HLA and the Pharmacogenomics of Drug Hypersensitivity
      • Abstract
      • 21.1 Overview
      • 21.2 Introduction
      • 21.3 Classification of Drug Hypersensitivity Syndromes
      • 21.4 Immunopathogenesis of Drug Hypersensitivity Syndromes
      • 21.5 HLA and Hypersensitivity Reactions
      • 21.6 Stratified Approaches to Prevent Drug Hypersensitivity and Their Translation into Clinical Medicine
      • 21.7 The Future Direction of Stratified Medicine in Drug-Induced Hypersensitivity
      • Acronyms
      • References
    • Chapter 22. Drug-Induced Liver Injury
      • Abstract
      • 22.1 Overview
      • 22.2 Epidemiology and Public Health Impact
      • 22.3 Etiology
      • 22.4 Pharmacogenomics and Stratified Medicine in DILI
      • 22.5 Difficulties in Identifying Biomarkers for DILI
      • 22.6 DILI-Associated Genetic Variants
      • 22.7 Utility of Dili Risk Variants in the Clinic
      • 22.8 Future Directions
      • 22.9 Conclusions
      • References
    • Chapter 23. Hemostasis and Anticoagulants
      • Abstract
      • 23.1 Overview
      • 23.2 Hemostasis
      • 23.3 Indications for Anticoagulation
      • 23.4 Parenteral Anticoagulants
      • 23.5 Oral Anticoagulants
      • 23.6 Conclusion and Directions for Future Research
      • References
    • Chapter 24. Pharmacogenomics of Warfarin
      • Abstract
      • 24.1 Overview
      • 24.2 Pharmacology of Warfarin
      • 24.3 Nongenetic Factors Affecting Warfarin Dose Requirement
      • 24.4 Genes with Major Effects on Warfarin Dose Requirement
      • 24.5 Additional Pharmacogenomic Factors Affecting Warfarin Dosage
      • 24.6 Application of Pharmacogenomics to Warfarin Prescription
      • 24.7 Conclusion and Future Research Directions
      • References
    • Chapter 25. Pharmacogenomics of Clopidogrel
      • Abstract
      • 25.1 Overview
      • 25.2 Clopidogrel Response Variation
      • 25.3 Genetic Dissection of Clopidogrel Response
      • 25.4 Current Status
      • 25.5 Conclusions and Future Directions
      • Abbreviations
      • References
    • Chapter 26. Pharmacogenetics of Antidepressant Drugs
      • Abstract
      • 26.1 Overview
      • 26.2 Candidate Gene Studies
      • 26.3 Genome-Wide Approaches
      • 26.4 Conclusion
      • Glossary
      • Acronyms and Abbreviations
      • References
    • Chapter 27. Personalized Medicine of Alzheimer’s Disease
      • Abstract
      • 27.1 Overview
      • 27.2 Toward a Personalized Medicine for Dementia and Neurodegenerative Disorders
      • 27.3 Genomics of Alzheimer’s Disease
      • 27.4 Pathogenic Events
      • 27.5 Biomarkers and Comorbidity
      • 27.6 Therapeutic Strategies
      • 27.7 Pharmacogenomics
      • 27.8 Future Perspective
      • 27.9 Conclusion
      • Appendix A
      • Appendix B
      • References
    • Chapter 28. Asthma
      • Abstract
      • Acknowledgments
      • 28.1 Overview
      • 28.2 Clinical Aspects
      • 28.3 Asthma Pathophysiology
      • 28.4 Current Management of Asthma
      • 28.5 Stratified Medicine for Asthma
      • 28.6 Drug Development in Asthma and Emerging Targets
      • 28.7 Conclusions and Future Directions
      • References
    • Chapter 29. Rheumatoid Arthritis
      • Abstract
      • 29.1 Overview
      • 29.2 Pharmacogenetics of Nonbiologic DMARDs
      • 29.3 Pharmacogenetics of Biologic DMARDS
      • 29.4 Conclusions and Future Directions
      • References
    • Chapter 30. Pharmacogenomics of Oral Antidiabetic Drugs
      • Abstract
      • 30.1 Overview
      • 30.2 Genetic Basis of Diabetes
      • 30.3 Management of Diabetes
      • 30.4 The Need for Pharmacogenomics and Stratified Medicine
      • 30.5 Genetic Variants Associated with Response to Oral Hypoglycemic Agents
      • 30.6 Stratified Oral Antidiabetic Medicine: Pharmacogenomics Application
      • 30.7 Conclusions: Future Perspectives
      • Abbreviations
      • References
    • Chapter 31. Genomics and Pharmacogenomics of Lipid-Lowering Therapies
      • Abstract
      • 31.1 Overview
      • 31.2 Lipid Metabolism
      • 31.3 Lipids and CVD Risk, Epidemiology, and Public Health Impact
      • 31.4 Genetic Basis of Lipid Disorders and Lipid Levels
      • 31.5 Conclusion and Future Directions
      • References
    • Chapter 32. Hypertension Pharmacogenomics
      • Abstract
      • 32.1 Overview
      • 32.2 Epidemiology and Public Health Impact
      • 32.3 Genetic Basis of Hypertension
      • 32.4 Need for Stratified Approaches to Treatment with Antihypertensives
      • 32.5 Pharmacogenomics of Blood Pressure Response to Antihypertensive Drugs
      • 32.6 Pharmacogenomics of Antihypertensive Treatment—Related Outcomes
      • 32.7 Future Perspectives
      • References
    • Chapter 33. QTc and Sudden Cardiac Death
      • Abstract
      • 33.1 Overview
      • 33.2 Genetic Syndromes
      • 33.3 Drug-Induced Variation in QTc
      • 33.4 Public Health Impact
      • 33.5 QTc in New Drug Discovery and Drug Safety
      • 33.6 Pharmacogenomic Studies
      • 33.7 Future Directions
      • Glossary
      • Acronyms and Abbreviations
      • References
      • Suggested Websites
    • Chapter 34. Stratified Medicine for Pancreatic Cancer
      • Abstract
      • 34.1 Overview
      • 34.2 Current Treatment Paradigm
      • 34.3 Stratified Therapeutic Approach
      • 34.4 Preclinical Models of Pancreatic Cancer
      • 34.5 Central Knowledge Database
      • 34.6 Biorepository and Privacy Issues
      • 34.7 Conclusion
      • References
    • Chapter 35. Pharmacogenomics in Anesthesia
      • Abstract
      • 35.1 Overview
      • 35.2 Pharmacokinetic Pharmacogenetics in Anesthesia
      • 35.3 Pharmacodynamics
      • 35.4 Conclusion
      • References
    • Chapter 36. Tuberculosis
      • Abstract
      • 36.1 Overview
      • 36.2 TB Etiology and Natural History
      • 36.3 Burden of TB
      • 36.4 Burden of TB Among Children
      • 36.5 TB Diagnosis
      • 36.6 Chemotherapy for TB
      • 36.7 Risk Factors: Genetics, HIV, Diabetes, and Smoking
      • 36.8 TB in Children
      • 36.9 Pharmacogenomics of TB
      • 36.10 Pharmacogenomics and TB
      • 36.11 Conclusion
      • References
    • Chapter 37. Hepatitis C Virus
      • Abstract
      • Acknowledgments
      • 37.1 Overview
      • 37.2 IL28B Polymorphism and HCV Outcomes
      • 37.3 ITPA Polymorphisms and Ribavirin-Induced Hemolytic Anemia
      • 37.4 Genetic Determinants of Liver Fibrosis Progression
      • 37.5 Clinical Translation
      • 37.6 Conclusion
      • Disclosures
      • Abbreviations
      • References
    • Chapter 38. Pharmacogenomics of Antifungal Agents
      • Abstract
      • 38.1 Overview of Antifungal Therapy
      • 38.2 Public Health Impact of Fungal Diseases
      • 38.3 The Need for Pharmacogenomics and Stratified Medicine
      • 38.4 Genetic Variability Associated with Antifungal Drugs
      • 38.5 Current Successes in Stratified Medicine
      • 38.6 Future Perspectives
      • References
    • Chapter 39. Advances in Understanding and Treatment of Human African Trypanosomiasis: Divergent Diseases Caused by Distinct Parasites
      • Abstract
      • 39.1 Overview
      • 39.2 The Genetics of Trypanosome Lytic Factors and Parasite Factors Enabling Protection Against Lysis
      • 39.3 Immune Responses and Immunoavoidance
      • 39.4 Pathologies Associated with Hat
      • 39.5 Diagnosis of Hat
      • 39.6 Staging the Disease
      • 39.7 Treatment
      • 39.8 Conclusions and Future Perspectives
      • Glossary
      • References
  • Part 8: Implementation and Regulatory
    • Chapter 40. Implementing Clinical Pharmacogenetics: Point-of-Care and Pre-Emptive Testing
      • Abstract
      • 40.1 Overview
      • 40.2 Clinical Pharmacogenetics and Implementation
      • 40.3 Point-of-Care Pharmacogenetic Testing
      • 40.4 Pre-emptive Pharmacogenetic Testing
      • 40.5 Conclusion and Future Perspectives
      • References
    • Chapter 41. Ethical Considerations in Pharmacogenomic Testing and Research in Pediatrics
      • Abstract
      • 41.1 Overview
      • 41.2 Historical Perspective
      • 41.3 Ethical Significance of Benefit, Risk, and Uncertainty in Pediatric Pharmacogenomics
      • 41.4 Federal Regulations and National Healthcare Priorities Related to Pharmacogenomics
      • 41.5 Translation of Pharmacogenomics into the Clinical Setting
      • 41.6 Future Implications of Pharmacogenomics Testing in Children
      • 41.7 Conclusion
      • References
    • Chapter 42. PGx/Biomarker Utilization for Regulatory Decision Making
      • Abstract
      • 42.1 Introduction
      • 42.2 Regulatory Activities and Guidelines Relating to PGx/Biomarker
      • 42.3 Biomarker Qualification
      • 42.4 Clinical Trial Design and Drug Development Utilizing PGx/Biomarker
      • 42.5 Future Challenges
      • Disclaimer
      • Glossary
      • References
  • Part 9: Global Perspective
    • Chapter 43. Population Diversity and Pharmacogenomics in Africa
      • Abstract
      • Acknowledgments
      • 43.1 Overview
      • 43.2 Population Diversity in Africa
      • 43.3 Population Genetics, Diversity, Ancestry, and Admixture
      • 43.4 Pharmacogenomics in Africa
      • 43.5 Future Perspectives
      • 43.6 Conclusions
      • Glossary
      • References
    • Chapter 44. Pharmacogenomics in China
      • Abstract
      • Acknowledgments
      • 44.1 Overview
      • 44.2 Pharmacogenomics of Drug-Metabolizing Enzymes in Chinese Populations
      • 44.3 Pharmacogenomics of Drug Transporters in Chinese Populations
      • 44.4 Pharmacogenomics of Drug Receptors in Chinese Populations
      • 44.5 Pharmacogenomics of ION Channels in Chinese Populations
      • 44.6 Environmental Factors in Drug-Metabolizing Enzyme and Transporter Activity
      • 44.7 Translational Approaches to Pharmacogenomics in China
      • 44.8 Conclusion and Future Perspectives
      • References
    • Chapter 45. Pharmacogenomics in Brazil
      • Abstract
      • Acknowledgments
      • 45.1 Overview
      • 45.2 The Brazilian Pharmacogenetics Network–Refargen
      • 45.3 PGX of Immunosuppressants in Renal Transplant Patients
      • 45.4 PGx of Antipsychotics in Schizophrenic Patients
      • 45.5 Conclusions
      • References
    • Chapter 46. Pharmacogenomics in India
      • Abstract
      • 46.1 Overview
      • 46.2 Indian Population Structure and Diversity
      • 46.3 Frequency Distribution and Pattern of Genetic Variants of Pharmacogenes
      • 46.4 Pharmacogenetic Studies in India
      • 46.5 Conclusions and Future Directions
      • References
  • Glossary
  • Acronyms
  • Index

Details

No. of pages:
1118
Language:
English
Copyright:
© Academic Press 2014
Published:
Imprint:
Academic Press
eBook ISBN:
9780123868831
Hardcover ISBN:
9780123868824

About the Editor-in-Chief

Sandosh Padmanabhan

Dr Sandosh Padmanabhan is a Reader and Honorary Consultant Physician at the Institute of Cardiovascular and Medical Sciences, University of Glasgow. His research spans the genetics of cardiovascular traits, pharmacogenomics and stratified medicines and hypertension epidemiology.

Affiliations and Expertise

Clinical Senior Lecturer, Institute of Cardiovascular and Medical Sciences; College of Medical, Veterinary and Life Sciences; University of Glasgow; UK

Reviews

"…a comprehensive resource to understand this rapidly advancing field aiming to deliver the right drug at the right dose to the right patient at the right time."--Anticancer Research, January 2015

"This is an extremely useful resource for clinicians, scientists, or any individuals interested in an excellent review of the rapidly advancing field of pharmacogenomics and its increasing relevance for clinical practice. - Rating: 5 Stars"--Doody's.com, 03-Oct-14