Pharmacogenomics: An Overview

 

Gharge Deepali*, Bavaskar Sunil, Todkar Pavan and Dhabale Pandurang

Government College of Pharmacy, Karad, Tal- Karad, Dist- Satara, 415124

State - Maharashtra, India.

 

ABSTRACT:

To increase the drug response, the pharmacogenomics applicable in pharmacotherapy by studying genomic level of the human being pharmacogenomics examine the role of entire genome in both disease susceptibility and drug response; in an attempt to identify specific genes, human genetic variation RNA and protein expression differences, that are associated with specific diseases and that may be targets for new drugs. Pharmacogenomics show ability to explore not only drug metabolizing polymorphisms but also drug target polymorphism, drug transporter polymorphisms.

 

Many factors influence drug responses including age, gender, body weight, patient health, disease status, diet, smoking, alcohol, and exercise and drug interaction. However despite careful consideration of these factors, there is no guarantee that a given treatment will be effective. It is thought that a major cause for variability in drug responses lies in patient’s genetic makeup. Genetic variations can be used to explain inter individual differences in drug response.

 

Pharmacogenomics is the study of how individual’s genetic inheritance affects the body’s response to drugs. The term comes from the words pharmacology and genomics and is thus the intersection of pharmaceuticals and genetics.

 

Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person’s own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person’s response to medicines, but understanding an individual’s genetic makeup to be the key to creating personalized drugs with greater efficacy and safety.

 

KEY WORDS:  Pharmacogenomics, Individual’s genetic inheritance, genome, personalized drugs.

 

INTRODUCTION:

Pharmacogenetics is a well–established discipline, which studies the genetic basis of interindividual variability in the response to drug therapy.[1,4]  With the advent of genomic sciences, a paradigm shift has occurred from the study of individual genes and their corresponding proteins to an analysis of the whole: the genome, the transcriptome, the proteome, the metabolome, and further derivatives of –omics (cellome, phenome; create your own –omics specialty!). In contrast to the pervasive analytical reductionist approach, genomics represents an integrative approach an attempt to put all the pieces back together. Medical genetics and pharmacogenomics take center stage in this (re)emerging science philosophy.

 

Pharmacogenomics is defined as "the use of associations between the effects of drugs and genetic markers to develop genetic tests that can be used to fine-tune patient diagnosis and treatment”.[5] Researchers in the field of pharmacogenomics study genes that produce drug-metabolizing enzymes in the body. Utilizing an individual's genetic profile in prescribing medications for various diseases will prevent unwanted side-effects and allow drugs to work more efficiently.


Pharmacogenomics requires the analysis of an individual's genetic information and the comparison of that genetic information, along with reactions to specific drugs, to the information and reactions of others to determine which drugs most effectively treat a given disease or condition.[6]

 

Although pharmacogenomics is not yet widely used, this technology is likely to someday change the way physicians practice medicine and the expectations of patients in seeking treatment. Pharmacogenomics may not only benefit patients by improving physicians' ability to more accurately provide treatment for diseases and illnesses, but this new technology may potentially affect patients negatively by risking the individual's right to privacy. The issue of privacy arises as a result of the inherently personal nature of each individual's genetic makeup. [7] Some people may be reluctant to share this information with physicians and medical researchers, fearing that they or their family members will be discriminated against by insurers if they test positive for a genetic disease.

 

Each individual has genetic markers, which serve as points of reference. [8] These markers are DNA or protein sequences that are located on a specific region of a chromosome.[9] The developing technology behind pharmacogenomics utilizes these genetic markers to evaluate how drugs will react in an individual with a specific genetic profile. Pharmacogenomics seeks to determine variations in drug responses by monitoring genetic changes (alterations in genotype) or physical changes (alterations in phenotype) in individuals and groups of patients in order to determine the most efficient and least adverse treatment for disease. Pharmacogenomics, as a way of enabling physicians to better treat their patients, inherently involves comparison and analysis of a large number of genetic profiles. In order to best evaluate which course of treatment to follow, and more specifically which drug will work best for a patient's condition, the physician must be able to evaluate other patients' responses to treatment options or drugs available for that condition. To provide the most comprehensive access to genetic profiles, there must be a database containing that information which physicians can access to determine the likelihood of adverse drug reactions, side-effects, and efficacy. Disclosure of this type of personal information inevitably leads to privacy issues, as individuals are concerned about sharing their genetic profiles with the general population.

 

This new method of cataloguing and disseminating genetic information is likely to increase the privacy concerns already associated with genetic research and genetic testing. Several studies have shown concern among United States citizens regarding discrimination and loss of privacy as a result of sharing their genetic information, and many cite these concerns as reasons for not participating in medical research studies. [10] Pharmacogenomics requires the examination of large numbers of genetic profiles for success, but individuals will be reluctant to participate unless measures are taken to ensure confidentiality and restrict the possibility of discriminatory uses of genetic information. This comment will first set forth the technology of pharmacogenomics and its future applicability to medical treatment. Second, it will propose a solution to the privacy issues resulting from the development of a pharmacogenomics database. This comment seeks to create a template for federal legislation protecting an individual's right to privacy in light of the development of pharmacogenomics technology.

 

The technological development of pharmacogenomics, examined in Part II, requires a database to compare and catalog genetic profiles of individuals suffering from various conditions and undergoing treatment for those conditions. Establishing a database poses issues of confidentiality and privacy, as an individual's information is made available to the public, or at least to specific classes of professionals. [11] The Health Insurance Portability and Accountability Act ("HIPAA") is the current manifestation of federal protection of patient privacy rights in the United States, [12] but this legislation may not be enough to protect individuals with the creation of a pharmacogenomics database containing genetic profiles. Part III analyzes the inadequacies of HIPAA in light of the development of pharmacogenomics and increased usage of genetic databases. Part IV will discuss how federal law may be tailored to balance patient privacy and the dissemination of information for the public good. This comment proposes, as a primary solution to concerns about genetic privacy, federal legislation that expands the scope of HIPAA to specifically protect information compiled in a pharmacogenomics database, in addition to providing incentives for patients to contribute to the public welfare by sharing their genetic profiles.

 

Pharmacogenomics is the study of how an individual's genetic inheritance affects the body's response to drugs. The term comes from the words pharmacology and genomics and is thus the intersection of pharmaceuticals and genetics. Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a person's response to medicines, but understanding an individual's genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety.

 

Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genes, proteins, and single nucleotide polymorphisms.

 

HISTORICAL BACKGROUND

Pharmacogenomics has been around in some form since the 1930s. [13] In 1902, Archibald Garrod first asserted the hypothesis that genetic variations could cause adverse biological reactions when chemical substances were ingested. [14] He also suggested that enzyme [15] were responsible for detoxifying foreign substances, and that some people do not have the ability to eliminate certain foreign substances from the body because they lack enzymes required to break down these materials.

 

The first pharmacogenetic study took place in 1932, when the inability to taste a chemical compound known as phenylthiocarbamide was linked to an autosomal recessive trait. An autosome is a chromosome that does not participate in sex determination, and therefore refers to all the cells in the body except for sperm and eggs. Recessive traits are described as follows: each person has two genes that code for a particular trait one is inherited from the mother and one is inherited from the father. [16] If a person inherits two different alternative forms of a gene, called alleles, the trait that is expressed physically as a phenotype is the dominant trait, while the one not expressed is a recessive trait. Examples of recessive traits include hitchhikers thumb and blue eyes.

 

In the 1932 study, participants with two recessive alleles were unable to produce a particular enzyme that allowed them to taste the phenylthiocarbamide chemical. This determination that the inability to taste was linked to an autosomal recessive trait demonstrated that certain chemicals react differently depending on genetic predispositions.

 

In the 1940s and 1950s, scientists first began to note "variable drug responses" in people taking various preventive medications. [17] Drug reactions based on inherited traits were first recorded during World War II, when some soldiers developed anemia after receiving doses of the anti-malarial drug primaquine. Later studies confirmed that the anemia was caused by a genetic deficiency of the glucose-6-phosphate dehydrogenase enzyme. [18] Similar reactions to succinlcholine and isoniazid were studied, and revealed that deficiencies in enzymes led to an inability to metabolize those drugs. [19] After studying adverse drug reactions to primaquine, succinlcholine, and isoniazid, Arno Moltulsky [20] proposed in 1957 that inherited traits may not only lead to adverse drug reactions, but may also affect whether the drugs actually work.

 

In recent decades, further progress has been made in isolating genetic variations in major drug-metabolizing enzymes, including cytochrome P450. [21] Scientists first began to study cytochrome P450 when some patients experienced a severe decline in blood pressure while taking debrisoquin, an anti-hypertensive drug. The study revealed that these patients had two recessive alleles for the enzyme, resulting in an inability to metabolize the drug. Approximately ten percent of the population metabolizes cytochrome P450 poorly, experiencing adverse effects and reduced drug uptake when they take drugs in the family of chemicals metabolized by the enzyme. The evaluation of cytochrome P450 has led to the identification and characterization of many other drug-metabolizing enzymes.

 

Although pharmacogenomics continues to be a burgeoning field of technology, it is unclear where this new technology will ultimately lead. Currently, research in pharmacogenomics is primarily focused on preventing adverse drug reactions through the analysis of the relationship between drug-metabolizing enzymes and the chemical compounds that those enzymes break down. In the future, pharmacogenomics may also be used to determine which receptors are best equipped to transport particular chemical compounds into the cell for the purpose of treating a disease or condition. Such an application would allow greater "personalization" of medicine by tailoring drugs to an individual's genetic profile. Although evaluating receptor participation in drug uptake is a promising area of research, it is likely that research in the near future will continue to focus on the evaluation of polymorphisms [22] in drug-metabolizing enzymes. [23]

NEED OF PHARMACOGENOMICS

Pharmacogenomics (or toxicogenomics) as a recently emerged discipline stems from the fusion of pharmacogenetics (or toxicogenomics) with genomics. Enabled by high-throughput technologies in DNA analysis, genomics introduces a further dimension to individualized predictive medicine. Determining an individual's unique genetic profile in respect to disease risk and drug response will have a profound impact on understanding the pathogenesis of disease, and it may enable truly personalized therapy. This concept can be highlighted as "therapy with the right drug at the right dose in the right patient." Its urgency emerged in a recent survey of studies on adverse drug effects in hospitalized patients: adverse drug reactions may rank as the fifth leading cause of death in the United States. [24] Thus, it is anticipated that pharmacogenomics will play an integral role in disease assessment, drug discovery and development, and selection of the type of drug. Moreover, it may provide information useful to the selection of dosage regimen for an individual patient.

 

Medicine, as we move into the third millennium, still targets therapy to the broadest patient population that might possibly benefit from it, and it relies on statistical analysis of this population's response for predicting therapeutic outcome in individual patients.

 

Therapists of necessity make decisions about the choice of drug and appropriate dosage based on information derived from population averages. This "one drug fits all" approach could, with the fruits of pharmacogenomic research, evolve into an individualized approach to therapy where optimally effective drugs are matched to a patient's unique genetic profile. [25] This involves classifying patients with the same phenotypic disease profile into smaller subpopulations, defined by genetic variations associated with disease, drug response, or both. The assumption underlying this approach is that drug therapy in genetically defined subpopulations can be more efficacious and less toxic than in a broad population.

 

The concept underlying pharmacogenomics is that response to drug therapy is variable, in part because of genetic variation. Genetic variations that are common (occurring in at least 1% of the population) are known as polymorphisms, and mutations of a single nucleotide are known as single nucleotide polymorphisms (SNPs) [26] More than one-third of human genes have been found to be polymorphic. [27] A change in the nucleotide sequence of a gene can lead to a change in the amino acid sequence of the protein and altered enzymatic activity, protein stability, and binding affinities. [28, 29] Genetic variation can thus affect drug efficacy and safety when the mutations occur in proteins that are drug targets (e.g., receptors), are involved in drug transport mechanisms (e.g., ion channels), or are drug-metabolizing enzymes. [30]

 

The term "pharmacogenetics" refers to the interaction of one gene (typically one involved in drug metabolism) with a drug, while "pharmacogenomics" is a more general term that refers to the interaction between a drug and any gene, or multiple sites throughout the genome. [31]

 

Medical genetics aims at understanding health and disease from a molecular genetic perspective, and one of its main goals is to identify disease susceptibility genes. In contrast to single–gene Mendelian disorders (e.g., cystic fibrosis), most major diseases are multigenic, and hence, many gene variants affect disease processes, with varying penetrance. Over 250 genes have been identified for cardiovascular disease.[32, 33] It is understood but has yet to be proven that the spectrum of variant genes contributing to cardiovascular diseases has a significant impact on an individual's risk and disease progression. On the other hand variant genes can also determine the outcome of drug therapy, a subject area of pharmacogenomics. Some understand pharmacogenomics to provide the means for drug selection in the following sense:

• The right drug for the right disease

In contrast, pharmacogenetics is seen to optimize an individual's therapy by focusing on proteins (and the respective gene variants) directly interacting with the drug (e.g., CYP450). In other words:

• The right drug for the right patient

This distinction is specious as genes could fall into both categories – for example those encoding receptors. The overriding goal is to optimize therapy of the individual patient with the use of genetic–genomic information. Whether a gene affects the drug response directly or lies downstream of drug effects does not represent a fundamental distinction.

 

In the early excitement about unraveling the human genome, expectations for pharmacogenomics soared. Here are some of the lofty visions of how medicine and therapy will look like in the (not too distant) future.

• Most susceptibility genes will be known for all major diseases. Individuals will carry a gene chip with information on all relevant gene variants that serve to guide proper life styles and therapy.

• The gene chip will also contain an individual's genetic background relevant to drug therapy (e.g., genes involved in transport and metabolism) which further aids in the selection and dosage of drugs.

• Finding numerous disease susceptibility genes will lead to the discovery of hundreds, if not thousands of new drug targets, and hence, a wave of drug discovery.

• Genetic profiling may permit early intervention or even prevention of disease – arguably the most desirable goal.

 

THE TECHNOLOGY BEHIND PHARMACOGENOMICS

Understanding the scientific processes underlying the technology of pharmacogenomics requires a short cell biology lesson. Each living organism has a unique genetic profile comprised of genes that code for the production of proteins. Proteins known to affect drug metabolism fall into three categories:

(1) Proteins that degrade or activate chemical compounds;

(2) Proteins that interact with a target molecule to prevent drugs from binding to a receptor;

(3) Proteins that regulate metabolic pathways that affect drug function. [34]

 

Some proteins themselves act as receptors, and therefore receive chemical signals from outside the cell. These proteins transport molecules into and out of cells, thereby regulating which materials are allowed to enter the cell. [35] Receptors, by virtue of their gate-keeping function, determine which drugs can enter the cell and fight disease. [36] Receptors on the surface of cells vary depending on genotype, as DNA determines the characteristics of proteins. Because of this variance, people react differently to different medications, as one person's receptors may allow a chemical into the cell while another person's receptors may prevent the cell from absorbing that drug.

 

In addition to determining which chemicals to allow into the cell, some proteins serve to alter the shape of drug molecules, effectively turning them "on”. [37] Evaluating which genotypes allow chemicals to be turned on, and which keep the drugs "off," will allow physicians to determine the medications that will work for their patients. Geneticists can now identify single genetic markers in an individual's genetic profile that code for drug-interaction genes, which will ultimately increase physicians' ability to prescribe the appropriate medication without the risk of side-effects or the possibility of failed treatment.

 

PHARMACOGENOMICS VERSUS GENETIC TESTING

Pharmacogenomics is considerably different from genetic testing because it requires an evaluation of a person's entire genetic profile, not just the presence or absence of single genetic markers. [38] Genetic testing was previously conducted under the theory that most diseases were monogenic, meaning that one gene caused each disorder. Now, the general belief has shifted toward the concept of polygenic disorders, where multiple mutated genes contribute to a single disorder. Due to this shift in theory, genetic testing now involves analyses of multiple portions of the genome, but still does not require analysis of the complete genetic profile. Although both pharmacogenomics and genetic testing involve comparing genes to determine the likelihood of future disease, only pharmacogenomics compares whole genetic profiles to evaluate drug efficacy and potential adverse reactions.

 

The success of the pharmacogenomics technology therefore depends on compiling complete genetic profiles that will allow physicians to compare thousands of single nucleotide polymorphisms ("SNPs") [39] from one individual with those of another individual. A comparison of these markers across the entire genome will enable physicians and researchers to "screen groups of patients receiving a specific drug and then correlate good and poor drug efficacy and the occurrence of specific side effects with individual SNP markers." As a result of these comparisons, physicians and researchers may determine which genetic markers influence adverse drug reactions and which genetic markers increase drug efficacy.[40]

 

ANTICIPATED BENEFITS OF PHARMACOGENOMICS

·                  More Powerful Medicines

Pharmaceutical companies will be able to create drugs based on the proteins, enzymes, and RNA molecules associated with genes and diseases. This will facilitate drug discovery and allow drug makers to produce a therapy more targeted to specific diseases. This accuracy not only will maximize therapeutic effects but also decrease damage to nearby healthy cells. [41]

·                  Better, Safer Drugs the First Time
Instead of the standard trial-and-error method of matching patients with the right drugs, doctors will be able to analyze a patient's genetic profile and prescribe the best available drug therapy from the beginning. Not only will this take the guesswork out of finding the right drug, it will speed recovery time and increase safety as the likelihood of adverse reactions is eliminated. Pharmacogenomics has the potential to dramatically reduce the the estimated 100,000 deaths and 2 million hospitalizations that occur each year in the United States as the result of adverse drug response. [42]

·                  More Accurate Methods of Determining Appropriate Drug Dosages

Current methods of basing dosages on weight and age will be replaced with dosages based on a person's genetics --how well the body processes the medicine and the time it takes to metabolize it. This will maximize the therapy's value and decrease the likelihood of overdose.

·                  Advanced Screening for Disease
Knowing one's genetic code will allow a person to make adequate lifestyle and environmental changes at an early age so as to avoid or lessen the severity of a genetic disease. Likewise, advance knowledge of a particular disease susceptibility will allow careful monitoring, and treatments can be introduced at the most appropriate stage to maximize their therapy.

·                  Better Vaccines

Vaccines made of genetic material, either DNA or RNA, promise all the benefits of existing vaccines without all the risks. They will activate the immune system but will be unable to cause infections. They will be inexpensive, stable, easy to store, and capable of being engineered to carry several strains of a pathogen at once.

·                  Improvements in the Drug Discovery and Approval Process

Pharmaceutical companies will be able to discover potential therapies more easily using genome targets. Previously failed drug candidates may be revived as they are matched with the niche population they serve. The drug approval process should be facilitated as trials are targeted for specific genetic population groups --providing greater degrees of success. The cost and risk of clinical trials will be reduced by targeting only those persons capable of responding to a drug.

·                  Decrease in the Overall Cost of Health Care
Decreases in the number of adverse drug reactions, the number of failed drug trials, the time it takes to get a drug approved, the length of time patients are on medication, the number of medications patients must take to find an effective therapy, the effects of a disease on the body (through early detection), and an increase in the range of possible drug targets will promote a net decrease in the cost of health care.


CURRENT STATUS

To a limited degree. The cytochrome P450 (CYP) family of liver enzymes is responsible for breaking down more than 30 different classes of drugs. DNA variations in genes that code for these enzymes can influence their ability to metabolize certain drugs. Less active or inactive forms of CYP enzymes that are unable to break down and efficiently eliminate drugs from the body can cause drug overdose in patients. Today, clinical trials researchers use genetic tests for variations in cytochrome P450 genes to screen and monitor patients. In addition, many pharmaceutical companies screen their chemical compounds to see how well they are broken down by variant forms of CYP enzymes. [43]

 

Another enzyme called TPMT (thiopurine methyltransferase) plays an important role in the chemotherapy treatment of a common childhood leukemia by breaking down a class of therapeutic compounds called thiopurines. A small percentage of Caucasians have genetic variants that prevent them from producing an active form of this protein. As a result, thiopurines elevate to toxic levels in the patient because the inactive form of TMPT is unable to break down the drug. Today, doctors can use a genetic test to screen patients for this deficiency, and the TMPT activity is monitored to determine appropriate thiopurine dosage levels. [44]

 

ADVANCES IN THE FIELD

Pharmacogenomics can help overcome two prominent factors responsible for complications of today’s cancer chemotherapy. First, patients usually have variable responses to chemotherapy, muddling decisions as to which drugs or cocktail of drugs will be optimal. Second, the arsenal of drugs used in chemotherapy today usually has very narrow therapeutic indices.[45]

 

Application of pharmacogenomics can address therapeutic indices by predicting patient response and speeding up the rate of drug development and clinical trials. [44] Recognizing the polymorphisms associated with disease makes individualized treatments possible, which can lower risks of imprecise dosage.
Among the many diseases associated with variability in drug response, cancer has benefited the most from pharmacogenomics research. While environment, age, diet, and other external factors are important, hereditary aspects of cancer have also been found to contribute to the variability in drug response of patients undergoing chemotherapy. [46] The inherited genetic polymorphisms are associated with malfunctioning enzymes, including drug metabolizers, and take the form of DNA sequence mutations (deletions, repeats, insertions) and SNPs.
A prominent example of how such a polymorphism can result in a higher patient susceptibility to ADRs is found in the treatment of leukemia. As described earlier, patients genetically endowed with weakened versions of TPMT cannot receive the regular dosage of thiopurine agents that interfere with DNA replication in rapidly dividing cells. Leukemia patients with a TPMT polymorphism require a lowered dosage to prevent toxic side-effects because not enough TPMT is present to metabolize the drug. [46, 47]

 

Methods have been established to diagnose TPMT deficiency to address this identifiable risk in leukemia patients undergoing chemotherapy, and physicians are advised to use an alternative therapy or to reduce dosage levels thiopurine drugs. [45] This diagnostic step is particularly important for children with acute lymphatic leukemia, as thiopurine dosage optimization has been directly correlated with higher survival rates. [45, 46] As long-term chemotherapy can have many detrimental effects, a major project lead by researchers in Australia aims to apply pharmacogenomic tools to the risk assessment of children undergoing chemotherapy in order to establish a highly specific diagnostic ability. While screening for TPMT polymorphisms is quite logical, the genotype alone is inadequate for optimizing treatment because thiopurine metabolism is not simply black and white. Patients with completely normal alleles may require reduced dosage, and vice versa. [48]
For lung cancer, testing levels of mRNA expression of relevant genes now provide information about patients that helps doctors decide whether to use gemcitabine or pemetrexe, two different chemotherapy cocktails, alone or in combination.


Similar approaches have been adopted in other diseases such as asthma, in which several polymorphisms have been associated with variable responses from patients using the three major drug types: glucocorticosteroids, [49] leukotriene modifiers, and beta-agonists. Researchers who approach asthma patients located in places where such polymorphisms are prevalent will have the capacity to test, identify, and match specific patients to specific treatment plans. Pharmacogenomic tests are thus a major supplement for established diagnostic measures that are based on mere phenotypic features such as weight or levels of specific biomarkers in the blood. [50]

 

FUTURE RESEARCH AREAS

The technology for genomics research has become increasingly automated, less expensive, and more rapid, allowing for greater capacity to implement genetic tests with high predictive values for drug development and clinical care. [45] As today’s genetic analyses become increasingly comprehensive, an ever expanding database of SNPs is at scientists’ disposal for the matching of alleles to diseases – the first step in understanding variabilities in drug response.

 What is necessary now for genetic analysis of SNPs is the rapidly detection and discrimination of SNPs in patient samples. The polymerase chain reaction (PCR) is a highly effective tool for amplifying regions of the genome containing the desired SNPs, and many innovations have been implemented to increase the amplification capacity of PCR.

 

The latest innovation in PCR technology allows the simultaneous analysis of over 1,000 SNPs using haploid genetic material or DNA from sperm and eggs. [49] In addition to increasing the throughput of large-scale genetic analyses, this new system requires a considerably less amount of DNA than previous systems, making tests more practical on highly preserved samples which have low, degraded amounts of DNA, such as tissues from cancer biopsies. In short, the improvements of this new technology, including a simpler protocol, higher sensitivity, no specialized equipment, and fewer reagents, greatly facilitate large-scale SNP analyses on samples that were previously impossible.[51]

 The technologies for measuring levels of gene expression have also advanced rapidly, allowing for simultaneous measurements in the form of high-density oligonucleotide arrays. This technology for exploring entire genomes can study a much larger quantity of genes and also requires simpler procedures than previous methods, making it ideal for identifying candidate genes of complex diseases.

 Such lines of technology can provide the genetic information for making predictions that associate specific polymorphisms in a patient with a specific drug metabolizing enzyme or drug target [46]. Should that polymorphism be linked with a deficit, the patient may then be steered to a better route of treatment.

 

CHALLENGES

Genome analysis for all individuals - Rapid, automated methods must be developed to efficiently identify SNPs in the three-billion-base-pair genome that influence susceptibility to disease and individual drug response. [52] 

 

Studying the biology of genes involved in disease and drug reactions - It can take decades to study a gene's product, function and association to drug response.

 

New techniques need to prove their worth - SNP analysis and expression profiling are in their infancy, and few success stories used.

 

Complex diseases really are complex! - In reality, disease and drug response can involve hundreds of genes. Environmental factors such as age, nutrition and lifestyle can influence disease and drug response as well.

 

CONCLUSION:

Pharmacogenomics is a rapidly evolving science with the potential to revolutionize drug discovery and development. Scientist’s believe an individual genetic makeup is the key to create personalized drugs with greater efficacy and safety. Pharmacogenomics has the potential to personalize medical therapies. As pharmacogenomics becomes more advanced, physicians eventually will be able to prescribe medication based on an individual’s patient’s genotype, maximizing effectiveness while minimizing side effects. Thus pharmacogenomics is likely to have a major role in daily practice of medicine in near future. Pharmacogenomics combines traditional pharmaceutical sciences such as biochemistry with annotated knowledge of genes, proteins and single nucleotide polymorphisms. It is found that, this is cost-effective therapy. It gives therapy of right drug to the right disease to the right patient at the right dose.

 

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Received on 27.08.2009

Accepted on 30.09.2009     

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Research J. Pharmacology and Pharmacodynamics  2009; 1(2): 59-65