Pharmacogenomics
Encyclopedia
Pharmacogenomics is the branch of pharmacology
which deals with the influence of genetic
variation on drug response in patients by correlating gene expression
or single-nucleotide polymorphisms with a drug's efficacy
or toxicity
. By doing so, pharmacogenomics aims to develop rational means to optimize drug therapy, with respect to the patients' genotype
, to ensure maximum efficacy with minimal adverse effects
. Such approaches promise the advent of "personalized medicine
"; in which drugs and drug combinations are optimized for each individual's unique genetic makeup.
Pharmacogenomics is the whole genome
application of pharmacogenetics
, which examines the single gene interactions with drugs.
, Clopidogrel
, tamoxifen
, and warfarin
are examples of medications that follow this metabolic pathway. Patient genotypes are usually categorized into predicted phenotypes. For example, if a person receives one *1 allele each from mother and father to code for the CYP2D6 gene, then that person is considered to have an extensive metabolizer (EM) phenotype. An extensive metabolizer is considered normal. Other CYP metabolism phenotypes include: intermediate, ultra-rapid, and poor. Each phenotype is based upon the allelic variation within the individual genotype.
, tuberculosis
, asthma
, and diabetes.
In cancer treatment, pharmacogenomics tests are used to identify which patients are most likely to respond to certain cancer drugs. In behavioral health, pharmacogenomic tests provide tools for physicians and care givers to better manage medication selection and side effect amelioration. Pharmacogenomics is also known as companion diagnostics, meaning tests being bundled with drugs. Examples include KRAS
test with cetuximab
and EGFR
test with gefitinib
.
In cardio vascular disorders, the main concern is response to drugs including warfarin
, clopidogrel
, beta blocker
s, and statin
s.
Many people take medications called SSRIs, or selective serotonin reuptake inhibitors, for different psychiatric disorders. Many of the medications are metabolized by CYP450 enzymes, including fluoxetine, paroxetine, and citalopram. GeneSightRx, a test provided by AssureRx Health, is an example of a product that provides information to health care providers about an individual patient’s genetic variability in response to multiple antidepressant and antipsychotic medications. Health care providers can use this information to help determine which medications maximize benefits while minimizing side effects.
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
which deals with the influence of genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
variation on drug response in patients by correlating gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
or single-nucleotide polymorphisms with a drug's efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
or toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
. By doing so, pharmacogenomics aims to develop rational means to optimize drug therapy, with respect to the patients' genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
, to ensure maximum efficacy with minimal adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
. Such approaches promise the advent of "personalized medicine
Personalized medicine
Personalized medicine is a medical model emphasizing in general the customization of healthcare, with all decisions and practices being tailored to individual patients in whatever ways possible...
"; in which drugs and drug combinations are optimized for each individual's unique genetic makeup.
Pharmacogenomics is the whole genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
application of pharmacogenetics
Pharmacogenetics
The terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive...
, which examines the single gene interactions with drugs.
Drug metabolism
There are several known genes which are largely responsible for variances in drug metabolism and response. The most common are the cytochrome P450 (CYP) genes, which encode enzymes that influence the metabolism of more than 80 percent of current prescription drugs. CodeineCodeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, Clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
, tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
, and warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
are examples of medications that follow this metabolic pathway. Patient genotypes are usually categorized into predicted phenotypes. For example, if a person receives one *1 allele each from mother and father to code for the CYP2D6 gene, then that person is considered to have an extensive metabolizer (EM) phenotype. An extensive metabolizer is considered normal. Other CYP metabolism phenotypes include: intermediate, ultra-rapid, and poor. Each phenotype is based upon the allelic variation within the individual genotype.
Applications
Pharmacogenomics has applications in illnesses like cancer, cardio vascular disorders, depression, bipolar disorder, attention deficit disorders, HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, and diabetes.
In cancer treatment, pharmacogenomics tests are used to identify which patients are most likely to respond to certain cancer drugs. In behavioral health, pharmacogenomic tests provide tools for physicians and care givers to better manage medication selection and side effect amelioration. Pharmacogenomics is also known as companion diagnostics, meaning tests being bundled with drugs. Examples include KRAS
KRAS
GTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene. Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways...
test with cetuximab
Cetuximab
Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...
and EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
test with gefitinib
Gefitinib
Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...
.
In cardio vascular disorders, the main concern is response to drugs including warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
, beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s, and statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s.
Many people take medications called SSRIs, or selective serotonin reuptake inhibitors, for different psychiatric disorders. Many of the medications are metabolized by CYP450 enzymes, including fluoxetine, paroxetine, and citalopram. GeneSightRx, a test provided by AssureRx Health, is an example of a product that provides information to health care providers about an individual patient’s genetic variability in response to multiple antidepressant and antipsychotic medications. Health care providers can use this information to help determine which medications maximize benefits while minimizing side effects.
See also
- GenomicsGenomicsGenomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
- PharmacogeneticsPharmacogeneticsThe terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive...
- ToxicogenomicsToxicogenomicsToxicogenomics is a field of science that deals with the collection, interpretation, and storage of information about gene and protein activity within particular cell or tissue of an organism in response to toxic substances. Toxicogenomics combines toxicology with genomics or other high throughput...
- ClinomicsClinomicsClinomics is the study of -omics data along with its associated clinical data. The term -omics generally refers to a study of biology. As an example, genomics is the study of the entire genome of an organism and was the first -omics term....
- Pharmacogenetics
- Population groups in biomedicineRace and healthRace and health research, often done in the United States, has found both current and historical racial differences in the frequency, treatments, and availability of treatments for several diseases. This can add up to significant group differences in variables such as life expectancy...