Category Archives: Pharmacogenomics

Dedication

List of Contributors

Preface

Chapter 1. Principles of Pharmacogenomics: Pharmacokinetic, Pharmacodynamic, and Clinical Implications

Objectives

Introduction

Cytochrome P-450 Enzymes

Non-CYP-450 Drug Metabolizing Enzymes

Polymorphisms in Drug Transporter Genes

Drug Target Genes

Conclusion

Questions for Discussion

References

Chapter 2. Translating Pharmacogenomic Research to Therapeutic Potentials

Objectives

Introduction

Implementation of Biomarkers in Clinical Practice

Incorporating Pharmacogenomics intoDrugDevelopment

Conclusion

Questions for Discussion

References

Chapter 3. Governmental and Academic Effortsto Advance the Field ofPharmacogenomics

Objectives

Introduction

The Role of the National Institutes of Health

The Role of the Food and Drug Administration and OtherInternational Government Agencies

Activities of Non-U.S. Agencies

Conclusion

Questions for Discussion

References

Chapter 4. Pharmacogenomics in Cancer Therapeutics

Objectives

Introduction

Role of Oncology Biomarkers

Concepts in Targeted Cancer Therapy

Oncology in the Postgenomic Era

Challenges in Drug Development and Cancer Trials

Seeking Pharmacogenomic Value

Questions for Discussion

References

Chapter 4A. A Look to the Future: CancerEpigenetics

Learning Objectives

Introduction

Histone Modification

DNA Methylation

Noncoding RNA (ncRNA)

Conclusion

Questions for Discussion

References

Chapter 5. Pharmacogenetics in Cardiovascular Diseases

Objectives

Introduction

Pharmacogenomics of Antiplatelet Agents

Warfarin Pharmacogenomics

Other Genetic Contributions to Warfarin Dose Variability and Response

Trials and Tribulations of Pharmacogenomics of Agents Used to Treat Dyslipidemia

Pharmacogenomic Potential in Heart Failure

Genetic Influences of Drug-Induced Arrhythmia

Conclusion

Discussion Points

Discussion Questions

References

Chapter 5A. A Look to the Future: Cardiovascular Pharmacoepigenetics

Learning objectives

Introduction

Opportunities

Challenges

Conclusion

Questions for Discussion

References

Chapter 6. Pharmacogenomics in Psychiatric Disorders

Objectives

Introduction

Polymorphisms in Proteins that Affect Drug Concentrations

Polymorphisms in Proteins that Mediate Drug Response

Application of Pharmacogenomics in Psychiatry

Conclusion

Questions for Discussion

References

Chapter 6A. A Look to the Future: Epigenetics in Psychiatric Disorders and Treatment

Objectives

Nature and Nurture Both Contribute to the Etiologies of Psychiatric Disorders

Epigenetic Processes Are Likely to Contribute to the Biochemical Basis of Nurture

Epigenetic Dysfunction Has Been Linked to Psychiatric and Neurological Disorders

Epigenetic Processes May Be Critical to Treatment Response in Psychiatric Disorders

Epigenetic Variation of Genes Regulating Pharmacokinetic Processes Is Likely to Influence Treatment Response

Epigenetic Modifications of Drug Transporters

Epigenetics and Adverse Drug Reactions

Limitations of Epigenetic Biomarkers in Psychiatry

Conclusion

Questions for Discussion

References

Chapter 7. The Role of Pharmacogenomics in Diabetes, HIV Infection, and Pain Management

Objectives

Introduction

Diabetes Overview

Type 2 Diabetes Pharmacogenomics

Challenges and Opportunities of Pharmacogenomics in Diabetes

Pharmacogenomics and HIV

Pharmacogenomics and Pain Control

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Pharmacogenomics - 1st Edition - Elsevier

General Description, Overview, and Opportunities

Pharmacogenomics has increasingly become an area of interest to clinicians because of the potential to tailor pharmacotherapy based on genetic variations in patients. Pharmacogenomics is one of the key aspects of personalized medicine, focusing on how an individual's DNA affects the way they respond to medications. All individuals have different genetic make-up so they respond differently to the same medication. Based on this insight, pharmacogenomics allows customized treatment for a wide range of health problems including; cardiovascular disease, Alzheimer's disease, cancer, HIV/AIDS, and asthma. Often, drug choice and dosage require experimentation (trial and error) in order to find the best treatment option. With pharmacogenomics testing, the need for this experimentation is decreased. As a result, the process becomes faster and more cost-effective and the possibility of adverse events caused by the wrong drug choice or dosage is significantly reduced.

One avenue for implementing pharmacogenomic is through medication therapy management (MTM), where pharmacists assess and evaluate a patient's complete medication therapy regimen. By gathering key pieces of information, e.g. which medications and supplements a patient is currently taking, pharmacists can assess current treatment and suggest alternative therapies.

As medication experts and POC service providers, pharmacists can educate physicians and patients and perform the actual sample collection to be utilized for genetic testing. The broad application of pharmacogenomics to personalized medicine will improve patient outcomes and lower healthcare costs.

Test Features

Pharmacies require a lab partner to provide clinically relevant data and interpret results for physicians. Most tests screens all well-established pharmacogenomics genes in a single, cost-effective test. Results are delivered quickly via intuitive, clinically relevant, medically actionable report. The data provides lifetime utility of data, thereby decreasing the need for future testing.

Community pharmacists routinely perform point of care services and can assist patients by:

Performing a buccal swab in minutes

Send the collected DNA to the lab

Interpret results and discuss with physicians

Contact the patient to explain the results and any changes in therapy

Companies

Pharmacist Resources and Training

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Pharmacogenomics - ncpanet.org

PGRN-Hub will encourage and support participation of all investigators with an interest in precision medicine through establishment of an efficient and innovative infrastructure that promotes scientific exchange through the following aims:

Aim 1.Provide support and infrastructure for PGRN meetings, conference calls and webinars that use information technologies and novel meeting activities to enhance communication and scientific exchange. In particular, we will provide logistical and technical support for (a) at least two PGRN annual meetings at designated PGRN sites and (b) regular conference calls and webinars.

Aim 2.Establish a PGRN Virtual Home to enhance and promote communications among PGRN members and with scientific and public audiences while attracting new membership. In particular, we will (a) develop and promote a web interface to unify, organize, and display all PGRN resources and activities at pgrn.org; (b) host lectures and display professional-quality presentations that highlight up-to-date PGRN accomplishments; and (c) establish an intranet to handle PGRN meeting logistics and to support PGRN webinars and internal collaborations.

Aim 3.Promote a collaborative and synergistic network by (a) incorporating networking opportunities into our meetings; (b) soliciting open proposals to develop and incubate new ideas for collaborations; and (c) providing access to information from key resources that will support the conduct of the proposed collaborative projects including PGRN Enabling Resources such as RPGEH.

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PGRN Hub - PGRN Hub

Intermountain Precision Genomics Core Laboratory announced today it is expanding RxMatch. The pharmacogenomics service the study of how genes affect a patients response to medication will be made available to all Intermountain Healthcare providers.

The growth of the effort is indicative of how precision medicine programs across the world are taking off like never before, fueled by the adoption of early diagnosis, an increasing number of adverse drug reaction cases, high prevalence of chronic diseaseand advancements in genetic science.

The global precision medicine market is expected to reach $141.7 billion by 2026, according to a recent report by BIS Research.

The Intermountain lab launched RxMatch as an antidepressant panel in September 2017, the RxMatch Comprehensive Panel introduced today expands the gene targets from 36 to 97.

The panel includes opioids, statins, immune-suppressants, antidepressants and many more. Intermountain will integrate the resulting genomic medicine into clinical care while it also manages the information obtained through genomic sequencing, according to Intermountain.

The objective of this project is to provide the most comprehensive and evidence-based information to the physician," David Loughmiller, laboratory manager for Intermountain Precision Genomics, said in a statement. The result, Loughmiller noted, is decreasing the amount of time and money spent to achieve the correct medication.

The results are used to guide proper dosage based on a patients specific DNA genotype, Tom Neuwerth, clinical technology consultant for Intermountain Precision Genomics Lab, added. Small genetic variations impact how a patient metabolizes and responds to drugs. Our test helps ordering providers prescribe the right medication, at the right dose, at the right time.

Patients supply DNA samples using cheek swabs collected by their physicians. Once samples are received, the lab makes comprehensive reports available within a week.

Intermountains announcement comes just three days ahead of the HIMSS Precision Medicine Summit, slated for May 18-19, 2018 in the nations capital.

Twitter: @Bernie_HITNEmail the writer: bernie.monegain@himssmedia.com

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Intermountain lab expands precision medicine with ...

PharmacogenomicsChoosing the right medication at the right dose for each patient

April 16, 2018

Did you know ... that the sequence of your genome can determine how you respond to certain medications?

Understanding pharmacogenomics, or tailoring a person's medications based on their genome, would not be possible without sequencing the genomes of many people and comparing their responses to medicines.

Oneof the most important uses for DNA sequencing is not to just sequence one human genome - but rather to sequence many human genomes to understand how genomic differences relate to different traits. Some such traits reflect physical characteristics (like eye color), whereas others can be used to help in the clinical care of patients. Scientists in the field of pharmacogenomics study how specific variants in your genome sequence influence your response to medications.

In order for our bodies to use some medicines properly, the cells in our bodies must make a few chemical changes that convert them into an active form, just like we do when we eat food. Then, these active forms of the medicine must get to the right places in the body or inside cells to do the job that we want them to do. If we want to make sure this happens, it makes sense that we would target our bodies' pathways involved in changing the medicine's form or in getting medicines to the right places. For example, you probably know someone who takes an antidepressant. Many of these medicines get to the right places by interacting with a protein called ABCB1,which works like a traffic cop on the outside of your cells.

Given ABCB1's important role in controlling traffic, you might imagine that if someone has a genomic variant that changes the shape or function of their ABCB1 protein, they might have a different response than usual to any number of medicines. We now know that is the case for some antidepressants, as well as other medications like statins for cholesterol and certain chemotherapy medicines. As a result, there are at least 18 pharmacogenomic tests for variants in ABCB1 listed in the NIH's Genetic Test Registry, with suggestions that you be tested for these variants to help determine the correct dose for certain medications.

Video courtesy of Mayo Clinic

Healthcare professionals and researchers are constantly seeking both to optimize medical treatments and to avoid adverse (or negative) reactions to treatments, which are estimated to affect between 7 percentand 14 percentof hospitalized patients. This makes adverse reactions a large cause of added days spent in a hospital, and the fourth leading cause of death in the United States.

One scary example of such an adverse reaction is Stevens-Johnson syndrome (SJS), a severe allergic reaction also called "scalded skin syndrome." It can be caused by infections, but also by very common medications like ibuprofen, anti-seizure medicines, or antibiotics. Patients may go from taking two pain pills to ending up in the hospital burn unit fighting for their lives if SJS progresses to a worse condition called toxic epidermal necrolysis (TEN). TEN is diagnosed when patients have shed at least one-third of the skin off of their bodies. Needless to say, anything we can do to prevent this allergic reaction is vitally important.

In Taiwan, married scientists Wen-Hung Chung (a physician) and Shuen-Iu Hung (an immunologist) noticed that SJS/TEN was much more common in patients taking carbamazepine, used to treat epilepsy and seizures, or allopurinol, used to treat gout. They showed that this was due to genomic variants in the HLA-B gene. Not surprisingly, this gene helps control the immune response. As a result of their work, the country of Thailand has implemented genomic testing before these medications are prescribed. The results of this "pharmacogenomic test" are used to decide whether it is safe to give a specific patient certain medicines, like carbamazepine or allopurinol. Thailand's government even covers the cost of this testing, and the frequency of SJS/TEN has been drastically reduced. We have since learned that different ancestries are associated with different HLA-B genomic variants, so countries may need to take different approaches to monitor which medications are most likely to be linked to SJS/TEN.

Video courtesy of Mayo Clinic

Understanding pharmacogenomics would not be possible without sequencing the genomes of many people and comparing them, and then comparing their response to medicines. But we have also learned that a person's genome sequence is not everything when it comes to medication responses. The human body is a very complicated machine, and the instructions written in our DNA are just part of the process.

There are some cases, as with the breast cancer treatment tamoxifen, where a small study showed that there might be a relationship between someone's response to the medicine and a variant in the CYP2D6 gene. However, this finding did not appear to be true in a larger study that involved many more people. That's why at this time, the U.S. Food and Drug Administration (FDA) labeling for tamoxifen does not recommend CYP2D6 pharmacogenomic testing, but the issue is still being reviewed as more research is conducted.

Another gene in the same CYP family, called CYP2C19, has variations which affect how your body can use clopidogrel (more commonly known as Plavix). This medication is a "blood thinner" which helps prevent blood clots, and thus reduces your risk of strokes or some heart attacks. If your CYP2C19 protein is not working properly due to a mutation in the gene, then you will not be able to process clopidogrel, and you need either a different dose or a different medication. As it turns out, these variants in CYP2C19 are also more common in those with Asian ancestry. Although testing for variants in this gene is also not routinely recommended, you may wish to speak with your healthcare provider about the test if you are given a prescription for clopidogrel, particularly if you have East Asian family members.

As the field of pharmacogenomics develops, more and more clinical trials will test for interactions between our genomes and the medicines we take. If you are interested in participating in such trials, you can search the ClinicalTrials.gov registry and look for ongoing studies with your condition. If you are curious whether any of your medications are known to be associated with pharmacogenomic information, check out the Pharmacogenomics Knowledge Database and speak with your medical care team. And, if you'd like to be part of a national effort along with one million other people that will involve pharmacogenomics research, look into the National Institute of Health's All of Us program.

Posted: April 16, 2018

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April 16: Pharmacogenomics - National Human Genome ...

The English-language neologism omics informally refers to a field of study in biology ending in -omics, such as genomics, proteomics or metabolomics. The related suffix -ome is used to address the objects of study of such fields, such as the genome, proteome or metabolome respectively. Omics aims at the collective characterization and quantification of pools of biological molecules that translate into the structure, function, and dynamics of an organism or organisms.

Functional genomics aims at identifying the functions of as many genes as possible of a given organism. It combines different -omics techniques such as transcriptomics and proteomics with saturated mutant collections.[1]

The suffix -ome as used in molecular biology refers to a totality of some sort; it is an example of a "neo-suffix" formed by abstraction from various Greek terms in -, a sequence that does not form an identifiable suffix in Greek.

The Oxford English Dictionary (OED) distinguishes three different fields of application for the -ome suffix:

The -ome suffix originated as a variant of -oma, and became productive in the last quarter of the 19th century. It originally appeared in terms like sclerome[2] or rhizome.[3] All of these terms derive from Greek words in -,[4] a sequence that is not a single suffix, but analyzable as --, the -- belonging to the word stem (usually a verb) and the - being a genuine Greek suffix forming abstract nouns.

The OED suggests that its third definition originated as a back-formation from mitome,[5] Early attestations include biome (1916)[6] and genome (first coined as German Genom in 1920[7]).[8]

The association with chromosome in molecular biology is by false etymology. The word chromosome derives from the Greek stems ()- "colour" and ()- "body".[8] While "body" genuinely contains the - suffix, the preceding -- is not a stem-forming suffix but part of the word's root. Because genome refers to the complete genetic makeup of an organism, a neo-suffix -ome suggested itself as referring to "wholeness" or "completion".[9]

Bioinformaticians and molecular biologists figured amongst the first scientists to apply the "-ome" suffix widely. Early advocates included bioinformaticians in Cambridge, UK, where there were many early bioinformatics labs such as the MRC centre, Sanger centre, and EBI (European Bioinformatics Institute). For example, the MRC centre carried out the first genome and proteome projects.

Lipidome is the entire complement of cellular lipids, including the modifications made to a particular set of lipids, produced by an organism or system.

Proteome is the entire complement of proteins, including the modifications made to a particular set of proteins, produced by an organism or system.

Glycomics is the comprehensive study of the glycome i.e. sugars and carbohydrates.

Foodomics was defined in 2009 as "a discipline that studies the Food and Nutrition domains through the application and integration of advanced -omics technologies to improve consumer's well-being, health, and knowledge"

Transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA, produced in one or a population of cells.

Inspired by foundational questions in evolutionary biology, a Harvard team around Jean-Baptiste Michel and Erez Lieberman Aiden created the American neologism culturomics for the application of big data collection and analysis to cultural studies.

The word comic does not use the "omics" suffix; it derives from Greek ()- (merriment) + -()- (an adjectival suffix), rather than presenting a truncation of ()-.

Similarly, the word economy is assembled from Greek ()- (household) + ()- (law or custom), and economic(s) from ()- + ()- + -()-. The suffix -omics is sometimes used to create names for schools of economics, such as Reaganomics.

Many omes beyond the original genome have become useful and have been widely adopted by research scientists. Proteomics has become well-established as a term for studying proteins at a large scale. "Omes" can provide an easy shorthand to encapsulate a field; for example, an interactomics study is clearly recognisable as relating to large-scale analyses of gene-gene, protein-protein, or protein-ligand interactions. Researchers are rapidly taking up omes and omics, as shown by the explosion of the use of these terms in PubMed since the mid '90s.[15]

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Omics - Wikipedia