Category Archives: Pharmacogenomics

Pharmacogenomics is the study of how genes affect a persons response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a persons genetic makeup.

Many drugs that are currently available are one size fits all, but they dont work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the bodys response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions.

The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.

The National Institute of General Medical Sciences offers a list of Frequently Asked Questions about Pharmacogenomics.

A list of Frequently Asked Questions about Pharmacogenomics is also offered by the National Human Genome Research Institute.

Additional information about pharmacogenetics is available from the Centre for Genetics Education as well as Genes In Life.

The Smithsonian National Museum of Natural Historys exhibit Genome: Unlocking Lifes Code discusses the utility of pharmacogenomics.

The Genetic Science Learning Center at the University of Utah offers an interactive introduction to pharmacogenomics. Another interactive tutorial is available from the PHG Foundation.

The American Medical Association explains what pharmacogenomics is and provides a list of practical applications.

The National Genetics and Genomics Education Centre of the National Health Service (UK) provides information about predicting the effects of drugs based on a persons genes.

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What is pharmacogenomics? - Genetics Home Reference

Pharmacogenomics (a portmanteau of pharmacology and genomics) is the study of the role of genetics in drug response. It deals with the influence of acquired and inherited genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with drug absorption, distribution, metabolism and elimination, as well as drug receptor target effects.[1][2][3] The term pharmacogenomics is often used interchangeably with pharmacogenetics. Although both terms relate to drug response based on genetic influences, pharmacogenetics focuses on single drug-gene interactions, while pharmacogenomics encompasses a more genome-wide association approach, incorporating genomics and epigenetics while dealing with the effects of multiple genes on drug response.[4][5][6]

Pharmacogenomics aims to develop rational means to optimize drug therapy, with respect to the patients' genotype, to ensure maximum efficacy with minimal adverse effects.[7] Through the utilization of pharmacogenomics, it is hoped that drug treatments can deviate from what is dubbed as the one-dose-fits-all approach. It attempts to eliminate the trial-and-error method of prescribing, allowing physicians to take into consideration their patients genes, the functionality of these genes, and how this may affect the efficacy of the patients current and/or future treatments (and where applicable, provide an explanation for the failure of past treatments).[4] Such approaches promise the advent of "personalized medicine"; in which drugs and drug combinations are optimized for each individual's unique genetic makeup.[8][9] Whether used to explain a patients response or lack thereof to a treatment, or act as a predictive tool, it hopes to achieve better treatment outcomes, greater efficacy, minimization of the occurrence of drug toxicities and adverse drug reactions (ADRs). For patients who have lack of therapeutic response to a treatment, alternative therapies can be prescribed that would best suit their requirements. In order to provide pharmacogenomic-based recommendations for a given drug, two possible types of input can be used: genotyping or exome or whole genome sequencing.[10] Sequencing provides many more data points, including detection of mutations that prematurely terminate the synthesized protein (early stop codon).[10]

Pharmacogenomics was first recognized by Pythagoras around 510 BC when he made a connection between the dangers of fava bean ingestion with hemolytic anemia and oxidative stress. Interestingly, this identification was later validated and attributed to deficiency of G6PD in the 1950s and called favism.[11][12] Although the first official publication dates back to 1961,[13] circa 1950s marked the unofficial beginnings of this science. Reports of prolonged paralysis and fatal reactions linked to genetic variants in patients who lacked butyryl-cholinesterase (pseudocholinesterase) following administration of succinylcholine injection during anesthesia were first reported in 1956.[1][14] The term pharmacogenetic was first coined in 1959 by Friedrich Vogel of Heidelberg, Germany (although some papers suggest it was 1957). In the late 1960s, twin studies supported the inference of genetic involvement in drug metabolism, with identical twins sharing remarkable similarities to drug response compared to fraternity twins.[15] The term pharmacogenomics first began appearing around the 1990s.[11]

There are several known genes which are largely responsible for variances in drug metabolism and response. The focus of this article will remain on the genes that are more widely accepted and utilized clinically for brevity.

The most prevalent drug-metabolizing enzymes (DME) are the Cytochrome P450 (CYP) enzymes. The term Cytochrome P450 was coined by Omura and Sato in 1962 to describe the membrane-bound, heme-containing protein characterized by 450nm spectral peak when complexed with carbon monoxide.[16] The human CYP family consists of 57 genes, with 18 families and 44 subfamilies. CYP proteins are conveniently arranged into these families and subfamilies on the basis of similarities identified between the amino acid sequences. Enzymes that share 35-40% identity are assigned to the same family by an Arabic numeral, and those that share 55-70% make up a particular subfamily with a designated letter.[17] For example, CYP2D6 refers to family 2, subfamily D, and gene number 6.

From a clinical perspective, the most commonly tested CYPs include: CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP3A5. These genes account for the metabolism of approximately 80-90% of currently available prescription drugs.[18][19] The table below provides a summary for some of the medications that take these pathways.

Also known as debrisoquine hydroxylase (named after the drug that led to its discovery), CYP2D6 is the most well-known and extensively studied CYP gene.[22] It is a gene of great interest also due to its highly polymorphic nature, and involvement in a high number of medication metabolisms (both as a major and minor pathway). More than 100 CYP2D6 genetic variants have been identified.[21]

Discovered in the early 1980s, CYP2C19 is the second most extensively studied and well understood gene in pharmacogenomics.[20] Over 28 genetic variants have been identified for CYP2C19,[23] of which affects the metabolism of several classes of drugs, such as antidepressants and proton pump inhibitors.[24]

CYP2C9 constitutes the majority of the CYP2C subfamily, representing approximately 20% of the liver content. It is involved in the metabolism of approximately 10% of all drugs, which include medications with narrow therapeutic windows such as warfarin and tolbutamide.[24][25] There are approximately 57 genetic variants associated with CYP2C9.[23]

The CYP3A family is the most abundantly found in the liver, with CYP3A4 accounting for 29% of the liver content.[20] These enzymes also cover between 40-50% of the current prescription drugs, with the CYP3A4 accounting for 40-45% of these medications.[12]CYP3A5 has over 11 genetic variants identified at the time of this publication.[23]

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Pharmacogenomics - Wikipedia, the free encyclopedia

What is Pharmacogenomics?

Why do people vary in their responses to prescribed medications, both with respect to how well the drug works and in their adverse reactions to it? The answer may lie in our genes. Scientists, doctors, and the pharmaceutical industry are working to customize medical treatments to suit our genetic signatures. The study of how our genetic variations interface with disease risk and responses to drugs is called pharmacogenomics.

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Investigate a pharmacogenetic test that is being used in the clinic today.

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See how tiny variations in a person's DNA can help predict drug response or disease risk.

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Consider how pharmacogenetics might remake the drug development process.

Supported by a Science Education Partnership Award (SEPA) Grant No. R25RR023288 from the National Center for Research Resources, a component of the NIH. The contents provided here are solely the responsibility of the authors and do not necessarily represent the official views of NIH.

APA format: Genetic Science Learning Center (2014, June 22) Pharmacogenomics. Learn.Genetics. Retrieved May 20, 2015, from http://learn.genetics.utah.edu/content/pharma/ MLA format: Genetic Science Learning Center. "Pharmacogenomics." Learn.Genetics 20 May 2015 <http://learn.genetics.utah.edu/content/pharma/> Chicago format: Genetic Science Learning Center, "Pharmacogenomics," Learn.Genetics, 22 June 2014, <http://learn.genetics.utah.edu/content/pharma/> (20 May 2015)

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Pharmacogenomics - Learn Genetics

Frequently Asked Questions About Pharmacogenomics

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Pharmacogenomics uses information about a person's genetic makeup, or genome, to choose the drugs and drug doses that are likely to work best for that particular person. This new field combines the science of how drugs work, called pharmacology, with the science of the human genome, called genomics.

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Until recently, drugs have been developed with the idea that each drug works pretty much the same in everybody. But genomic research has changed that "one size fits all" approach and opened the door to more personalized approaches to using and developing drugs.

Depending on your genetic makeup, some drugs may work more or less effectively for you than they do in other people. Likewise, some drugs may produce more or fewer side effects in you than in someone else. In the near future, doctors will be able to routinely use information about your genetic makeup to choose those drugs and drug doses that offer the greatest chance of helping you.

Pharmacogenomics may also help to save you time and money. By using information about your genetic makeup, doctors soon may be able to avoid the trial-and-error approach of giving you various drugs that are not likely to work for you until they find the right one. Using pharmacogenomics, the "best-fit" drug to help you can be chosen from the beginning.

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Doctors are starting to use pharmacogenomic information to prescribe drugs, but such tests are routine for only a few health problems. However, given the field's rapid growth, pharmacogenomics is soon expected to lead to better ways of using drugs to manage heart disease, cancer, asthma, depression and many other common diseases.

One current use of pharmacogenomics involves people infected with the human immunodeficiency virus (HIV). Before prescribing the antiviral drug abacavir (Ziagen), doctors now routinely test HIV-infected patients for a genetic variant that makes them more likely to have a bad reaction to the drug.

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FAQ About Pharmacogenomics

What is pharmacogenomics? Pharmacogenomics is the study of genetic variations that influence individual response to drugs. Knowing whether a patient carries any of these genetic variations can help prescribers individualize drug therapy, decrease the chance for adverse drug events, and increase the effectiveness of drugs.

Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with with an understanding of common DNA variations in the human genome. The most common variations in the human genome are called single nucleotide polymorphisms (SNPs). There is estimated to be approximately 11 million SNPs in the human population, with an average of one every 1,300 base pairs. An individual's response to a drug is often linked to these common DNA variations. In a similar manner, susceptibility to certain diseases is also influenced by common DNA variations. Currently, much of the research in the field of pharmacogenomics is focused on genes encoding either metabolic enzymes that can alter a drug's activity or defective structural proteins that result in increased susceptibility to disease.

Anticipated benefits of pharmacogenomics Pharmacogenomicshas the potential toprovide tailored drug therapy based on genetically determined variation in effectiveness and side effects. This will mean:

Practical applications of pharmacogenomics today Following are links to scientific abstracts that discuss practical applications of pharmacogenomics in cancer, depression, cardiovascular disease and drug metabolism:

Economic issues from molecule to marketplace Pharmacogenomics eventually can lead to an overall decrease in the cost of health care because of decreases in:

Additional resources

The Department of Energy (DOE) Human Genome Project Information - pharmacogenomics

International HapMap Project

National Institute of General Medical Science

Listing of federally-sponsored clinical trials in US

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Pharmacogenomics - American Medical Association

Pharmacogenomics Meaning
Video shows what pharmacogenomics means. The study of genes that code for enzymes that metabolize drugs, and the design of tailor-made drugs adapted to an individual #39;s genetic make-up.

By: ADictionary

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Pharmacogenomics Meaning - Video