Medical Epigenetics

**Selected for Doody’s Core Titles® 2024 in Clinical Genetics**

Medical Epigenetics, Second Edition provides a comprehensive analysis of epigenetics in health management, across a broad spectrum of disease categories and specialties, and with a focus on human systems, epigenetic diseases that affect these systems, and evolving modes of epigenetic-based treatment. Here, more than 40 leading researchers examine how each human system is affected by epigenetic maladies, offering an all-in-one resource on medical epigenetics not only for those directly involved with health care, but investigators in life sciences, biotech companies, graduate students, and others who are interested in applied aspects of epigenetics. Incorporating both diagnostic and prognostic epigenetic approaches, this volume also fully supports the application of epigenetics in precision medicine.

This second edition of Medical Epigenetics, a volume in the Translational Epigenetics series, has been fully revised to address recent advances in disease epigenetics and role of epigenetics in precision medicine, with all-new chapters on skin cancer epigenetics, network analysis in medical epigenetics, machine learning in epigenetic diseases, and clinical trials of epigenetics drugs.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Section A: Overview
Chapter 1: Advances in medical epigenetics
Abstract
Introduction
Basic principles of epigenetics
General medical aspects of epigenetics
Epigenetics of system disorders
Multisystem medical epigenetics
Bioinformatics of epigenetic medicine
Pharmacology of epigenetics
Therapeutic epigenetics
Medical epigenetics: Future prospects
Conclusion
Section B: General medical aspects of epigenetics
Chapter 2: Environmental epigenetic epidemiology
Abstract
Acknowledgment
Introduction
Malnutrition
Environmental pollutants
Substance abuse
Infection
Conclusions and perspectives
Abbreviations
Chapter 3: Lifestyle and preventive medical epigenetics
Abstract
Introduction
Impact of dietary pattern on the epigenome
Exercise and epigenetics
Environmental factors and epigenetic modification
Lifestyle modification as a preventive tool for medical epigenetics
Conclusion
Chapter 4: Environmental medical epigenetics: A review of epigenetically induced medical risks generated from exposures in our air, food, and personal products
Abstract
Introduction
Allergens
Secondhand cigarette smoke and vaping
Traffic-related air pollution
Trace metals
Heavy metals
Endocrine-disrupting chemicals
Pesticides and fungicides
Volatile organic compounds
Farm exposure
Diet
Conclusions/outstanding questions
Glossary
Chapter 5: Behavioral medical epigenetics
Abstract
Introduction
Impact of environmental factors on behavior
Animal models and studies of human behavior
Environmental stressors and epigenetic mediators of the stress response
Nonepigenetic and alternate mechanisms of stress
The HPA axis and the stress response
Glucocorticoid signaling and epigenetics
HPA axis genes: Genes that regulate glucocorticoid signaling
Chronic stress and glucocorticoid resistance
Glucocorticoid resistance and epigenetics
HPA axis genes: Genes that regulate tissue-specific processes
Environmental stressors and neurotransmitters
Interconnectivity of the neurotransmitter systems
The dopaminergic system
Behavioral disorders associated with the dopaminergic system
Evidence for glucocorticoid effect on dopaminergic transmission
Glucocorticoids and dopamine in drug addiction
Epigenetic mediators of glucocorticoids on dopamine-related behavior
Adrenergic and noradrenergic systems
Behavioral disorders associated with the adrenergic and noradrenergic system
Evidence for glucocorticoid effect on adrenergic and noradrenergic transmission
Epigenetic mediators of glucocorticoids on adrenaline- and noradrenaline-related behavior
The serotonergic (5-HT) system
Behavioral disorders associated with the serotonergic system
Evidence for glucocorticoid effect on serotonergic transmission
Epigenetic mediators of glucocorticoids on serotonin-related behavior
Glutamate and GABA systems
Behavioral disorders associated with the glutamate and GABA system
Evidence for glucocorticoid effect on glutamate and GABA system
Epigenetic mediators of glucocorticoids on glutamate and GABA-related behavior
Conclusion
Chapter 6: Medical epigenetics and twins
Abstract
Introduction
Monogenic disorders: Twin studies and the epigenetics of imprinting disorders
Twin studies and the epigenetics of multifactorial disorders
Caveats
Future directions
Conclusions
Chapter 7: Epigenetic biomarkers of disease
Abstract
Introduction
Epigenetic biomarkers
Epigenetic biomarkers in cancer
Methods for assessing epigenetic changes for biomarkers
Clinical application of epigenetic biomarkers
Future perspectives
Conclusion
Abbreviations
Chapter 8: Prognostic epigenetics
Abstract
Introduction
DNA methylation markers of cancer prognosis
Histone modifications as markers of cancer prognosis
Noncoding RNA prognostic markers in cancer
Prognostic epigenetic markers in nonmalignant pathology
The future
Conflict of interest statement
Section C: Epigenetics of system disorders
Chapter 9: Autoimmune disease and epigenetics
Abstract
Autoimmune disease overview
Epigenetics and autoimmunity
Environmental epigenetics
Xenobiotic-induced epigenetic changes and autoimmunity
Conclusions
Chapter 10: Epigenetics of pulmonary diseases
Abstract
Grants
Introduction
Epigenetic basics
Epigenetics in disease
Epigenetics in the lungs
Epigenetics in pulmonary diseases
Conclusion
Chapter 11: Cardiovascular disorders and epigenetics
Abstract
Introduction
Early heart development and the fetal origin of cardiovascular disease
Epigenetic involvement in cardiovascular risk factors
Epigenetics and cardiovascular disease
Epigenetic-based cardiovascular therapy
Conclusion
Chapter 12: Epigenomics of intestinal disease
Abstract
Acknowledgments
Introduction
Epigenetics and intestinal development
Intestinal homeostasis and the microbiota
Epigenetics, intestinal homeostasis, and the microbiota
Microbiota-derived metabolites
Diet and the intestinal epigenome
Colon cancer
Inflammatory bowel disease
Irritable bowel syndrome
Celiac disease
Therapeutics
Future directions
Glossary
Chapter 13: Epigenetics of skin disorders
Abstract
Acknowledgments
Immunologic skin diseases
Infectious skin diseases
Skin tumors
Skin aging
Conclusions
Abbreviations
Chapter 14: Epigenetics in bone and joint disorders
Abstract
Introduction
Epigenetic regulation of the immune system in rheumatic diseases
Epigenetics therapy in rheumatic diseases
miRNAs as biomarkers for rheumatology and bone diseases
Conclusions
Chapter 15: Epigenetics of muscle disorders
Abstract
Introduction
Atrial fibrillation
Fibromyalgia
Gastrointestinal disorders
Abbreviations
Chapter 16: Reproductive disease epigenetics
Abstract
Introduction
Gametogenesis
Male reproductive disorders
Female reproductive disorders
Placental syndromes
Human papillomavirus and cervical cancer
Summary
Chapter 17: Epigenetics in ocular medicine
Abstract
Introduction
Epigenetics and the eye
Epigenetics in ocular disease
Discussion and conclusions
Section D: Multi-system medical epigenetics
Chapter 18: Pediatric diseases and epigenetics
Abstract
Acknowledgments
Introduction
Specific syndromes and disorders whose genes are involved in the processes and mechanisms of epigenetic regulation of gene expression
Microdeletions and duplications of chromosomes
Disorders of genomic imprinting
Descriptions of particularly well-known syndromes involving parental imprinting
Known environmental exposures which are likely to have disturbances in epigenetic regulation
Developmental disorders that are likely to involve epigenetic mechanisms
Monozygotic twins
Preconception and periconception effects
Microbiome
Developmental origins of health and disease (DOHaD)
The application of epigenetic research to public health policy of the future
The future impact of epigenetics on pediatrics
Abbreviations
Chapter 19: Epigenetics of infectious diseases
Abstract
Acknowledgments
Introduction
Pathogen-induced epigenetic modifications in host cells
Epigenetic modifications in bacterial pathogens
Conclusions
Glossary
Chapter 20: Clinical utility of solid tumor epigenetics
Abstract
Acknowledgments
Epigenetic drugs
Liquid biopsy
Concluding remarks
Abbreviations
Chapter 21: Epigenetics in acute myeloid leukemia
Abstract
Introduction
Epigenetic regulation of the genome
Normal hematopoiesis
Acute myeloid leukemia
Environment
Genetic and cytogenetic anomalies
Epigenetics in acute myeloid leukemia
Epigenetic-based therapy
Conclusions
Chapter 22: Epigenetic regulation in cancer metastasis
Abstract
Overview of cancer metastasis
Epigenetic control
Molecular pathways of EMT
Anoikis resistance
Extravasation and colonization
Epigenome-wide big data analysis for mechanistic understanding of metastasis
Abbreviations
Chapter 23: Epigenetics in exercise science and sports medicine
Abstract
Acknowledgments
Introduction
General findings
Muscle tissue
Blood cells
Cardiovascular tissues
Brain
Other tissues
Conclusion
Abbreviations
Section E: Bioinformatics of epigenetic medicine
Chapter 24: Machine learning in epigenetic diseases
Abstract
Introduction
Fundamentals of machine learning
Machine learning applications in epigenetics
Performance and limitations of machine learning approaches
Summary
Section F: Pharmacology of epigenetics
Chapter 25: Epigenetics in toxicology and drug development
Abstract
Introduction
Epigenetics and diseases
Conclusion and future perspective
Disclaimer
Abbreviations
Chapter 26: Pharmacoepigenomics in neurodegenerative diseases
Abstract
Introduction
NDD-specific pharmacoepigenomic signatures
Epigenetic-modifying drugs for NDDs
Epigenetic regulation of pharmacokinetics and pharmacodynamics
Conclusion
Section G: Therapeutic epigenetics
Chapter 27: Therapeutics and DNA methylation inhibitors
Abstract
Introduction
Mechanism of action
Application of DNMT inhibitors
Other DNMT inhibitors
Conclusions
Chapter 28: Histone deacetylase inhibitors in medical therapeutics
Abstract
Introduction
Classification of histone deacetylases
Classification of HDAC inhibitors
HDAC inhibitors for the treatment of cancer
HDAC inhibitors for the treatment of heart diseases
HDAC inhibitors for the treatment of kidney disease
HDAC inhibitors for the treatment of idiopathic pulmonary fibrosis
HDAC inhibitors for the treatment of inflammatory bowel disease
HDAC inhibitors for the treatment of rheumatoid arthritis
HDAC inhibitors for the treatment of schizophrenia
HDAC inhibitors for the treatment of Parkinson’s disease
HDAC inhibitors for the treatment of diabetes mellitus
Safety issues with the use of HDAC inhibitors
Conclusions
Abbreviations
Chapter 29: Sirtuins as NAD+-dependent deacetylases and their potential in medical therapy
Abstract
Introduction
Sirtuins
Summary
Abbreviations
Chapter 30: Experimental approaches toward histone acetyltransferase modulators as therapeutics
Abstract
Introduction
Histone acetyltransferases
HATs in disease
HAT modulators
Therapeutic possibilities of HAT modulators
Conclusion
Chapter 31: Histone methylation modifiers in medical therapeutics
Abstract
Introduction
Enhancer of zeste homolog 2 (EZH2, KMT6A)
Disruptor of telomeric silencing like (DOT1L, KMT4)
Lysine-specific demethylase 1 (LSD1, KDM1A)
Targeting other histone methylation modifiers
Conclusions
Abbreviations
Glossary
Chapter 32: Modulation of noncoding RNAs (ncRNAs) and their potential role as therapeutics
Abstract
Introduction
Noncoding RNA in the regulation of gene expression
RNA activation
ncRNA as biomarkers of human disorders
Therapeutic potential of miRNA
siRNAs and saRNAs in clinical trials
Concluding remarks
Chapter 33: Nutrients and phytonutrients as promising epigenetic nutraceuticals
Abstract
Acknowledgments
Abbreviations
Introduction
Epigenetic mechanisms
Nutrients, phytonutrients, and epigenetics
Dietary phytochemicals and nutrients as modulators of DNA methylation and histone modifications
Dietary phytochemicals and nutrients as regulators of miRNAs
Epigenetic clinical trials with dietary phytochemicals and nutrients
Conclusions
Chapter 34: Epigenetics of pain management
Abstract
Introduction
Chronic pain states
Role of epigenetic mechanisms in chronic pain
Future approaches to exploit the role of epigenetics in chronic pain
Challenges and hurdles for epigenetic therapies
Conclusion
Chapter 35: Precision medical epigenetics
Abstract
Enabling technologies for precision epigenetic medicine
Epigenetic modifications contribute to gene expression variations
Epigenetic modifications contribute to drug response and prognosis
Novel cytosine modifications for precision medicine
Challenges and perspectives
Conclusions
Chapter 36: Epigenetics and regenerative medicine
Abstract
Introduction
Epigenetic defects in aged tissues
Epigenetic dysregulation in cognition and neurodegeneration
Epigenetic remodeling tools used in regenerative medicine therapeutics
Applications of epigenetic remodelers in regenerative medicine
Future promise for epigenetic medical therapy
Conclusion
Chapter 37: Stem cell epigenetics in medical therapy
Abstract
Introduction
Stem cells
Epigenetics of stem cells
DNA methylation
Histone modifications
Noncoding RNA
RNA modifications
Therapeutic prospects of stem cells
Summary
Glossary
Abbreviation
Chapter 38: The clinical landscape of HDAC inhibitors
Abstract
Nucleosome modification and transcriptional regulation
One to eleven: The human zinc-dependent HDACs
HDAC inhibitors—A pharmacological classification
Nonselective HDAC inhibitors
Nuclear isoform selective HDAC inhibitors
HDAC6 and HDAC8 isoform selective inhibitors
Dual mechanism HDAC inhibitors
Advanced clinical trials—Hematological cancers
Advanced clinical trials—Non-blood cancers
Advanced clinical trials—Beyond cancer
Summary
Section H: Medical epigenetics: Future prospects
Chapter 39: Epigenetics: Future prospective in human disorders and therapeutics
Abstract
Introduction
Epigenetics in stress and related disorders
Epigenetics in human chromosomal disorders
Future perspective
Chapter 40: Prospective advances in medical epigenetics
Abstract
Acknowledgments
Introduction
Prospective advances of DNA methylation in medical epigenetics
Prospective advances of histone modification in medical epigenetics
Prospective advances of noncoding RNAs in medical epigenetics
International Human Epigenome Consortium and epigenetical precision medicine
Limitations
Prospect
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Medical Epigenetics

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