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Handbook of Pharmacogenomics and Stratified Medicine
1st Edition - April 28, 2014
Editor: Sandosh Padmanabhan
Language: English
Hardback ISBN:9780123868824
9 7 8 - 0 - 1 2 - 3 8 6 8 8 2 - 4
eBook ISBN:9780123868831
9 7 8 - 0 - 1 2 - 3 8 6 8 8 3 - 1
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 t…Read more
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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.
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
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
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
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
No. of pages: 1118
Language: English
Edition: 1
Published: April 28, 2014
Imprint: Academic Press
Hardback ISBN: 9780123868824
eBook ISBN: 9780123868831
SP
Sandosh Padmanabhan
Dr. Sandosh Padmanabhan MD, PhD, FRCP, FAHA, FBHS, FBPhS is a Professor and Physician at the Institute of Cardiovascular and Medical Sciences, University of Glasgow. Dr. Padmanabhan completed his MBBS and MD at JIPMER, Pondicherry, India and was awarded the Gold Medal for MD General Medicine in 1995. His PhD thesis (1999-2003) on G-protein signaling in hypertension was awarded the Bellahouston Medal by the University of Glasgow in 2004, and he received the Austin Doyle Award from the International Society of Hypertension in 2004. Dr. Padmanabhan’s pharmacogenetic genome-wide linkage study led to a BHF Intermediate Fellowship (2006-2009), and he also led a genome wide association analysis of hypertension between 2008 and 2010, resulting in the discovery of a new gene and pathway for hypertension. Dr. Padmanabhan was a visiting fellow to the Broad Institute of Harvard and MIT (2010-2012). Currently, he is a Fellow of the Royal College of Physicians, the British Hypertension Society, and the American Heart Association. His active research areas span the genetics of cardiovascular traits, pharmacogenomics and stratified medicine, and hypertension epidemiology.
Affiliations and expertise
Professor of Cardiovascular Genomics and Therapeutics, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK
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