|
Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. The term pharmacogenetics is often used interchangeably with the term pharmacogenomics which also investigates the role of acquired and inherited genetic differences in relation to drug response and drug behavior through a systematic examination of genes, gene products, and inter- and intra-individual variation in gene expression and function.〔(【引用サイトリンク】 url=https://pharmacy.unc.edu/research/centers/center-for-pharmacogenomics-and-individualized-therapy )〕 In oncology, ''pharmacogenetics'' historically is the study of germline mutations (e.g., single-nucleotide polymorphisms affecting genes coding for liver enzymes responsible for drug deposition and pharmacokinetics), whereas ''pharmacogenomics'' refers to somatic mutations in tumoral DNA leading to alteration in drug response (e.g., KRAS mutations in patients treated with anti-Her1 biologics). == Predicting drug-drug interactions == Much of current clinical interest is at the level of pharmacogenetics, involving variation in genes involved in drug metabolism with a particular emphasis on improving drug safety. The wider use of pharmacogenetic testing is viewed by many as an outstanding opportunity to improve prescribing safety and efficacy. Driving this trend are the 106,000 deaths and 2.2 Million serious events caused by adverse drug reactions in the US each year. As such ADRs are responsible for 5-7% of hospital admissions in the US and Europe, lead to the withdrawal of 4% of new medicines and cost society an amount equal to the costs of drug treatment. Comparisons of the list of drugs most commonly implicated in adverse drug reactions with the list of metabolizing enzymes with known polymorphisms found that drugs commonly involved in adverse drug reactions were also those that were metabolized by enzymes with known polymorphisms (see Phillips, 2001). Scientists and doctors are using this new technology for a variety of things, one being improving the efficacy of drugs. In psychology, we can predict quite accurately which anti-depressant a patient will best respond to by simply looking into their genetic code. This is a huge step from our previous way of adjusting and experimenting with different medications to get the best response. Antidepressants also have a large percentage of unresponsive patients and poor prediction rate of ADRs (adverse drug reactions). In depressed patients, 30% are not helped by antidepressants. In psychopharmacological therapy, a patient must be on a drug for 2 weeks before the effects can be fully examined and evaluated. For a patient in that 30%, this could mean months of trying medications to find an antidote to their pain. Any assistance in predicting a patient’s drug reaction to psychopharmacological therapy should be taken advantage of. Pharmacogenetics is a very useful and important tool in predicting which drugs will be effective in various patients. The drug Plavix blocks platelet reception and is the second best selling prescription drug in the world, however, it is known to warrant different responses among patients. GWAS studies have linked the gene CYP2C19 to those who cannot normally metabolize Plavix. Plavix is given to patients after receiving a stent in the coronary artery to prevent clotting. Stent clots almost always result in heart attack or sudden death, fortunately it only occurs in 1 or 2% of the population. That 1 or 2% are those with the CYP2C19 SNP. This finding has been applied in at least two hospitals, Scripps and Vanderbilt University, where patients who are candidates for heart stents are screened for the CYP2C19 variants. Another newfound use of Pharmacogenetics involves the use of Vitamin E. The Technion Israel Institute of Technology observed that vitamin E can be used to in certain genotypes to lower the risk of cardiovascular disease in patients with diabetes, but in the same patients with another genotype, vitamin E can raise the risk of cardiovascular disease. A study was carried out, showing vitamin E is able to increase the function of HDL in those with the genotype haptoglobin 2-2 who suffer from diabetes. HDL is a lipoprotein that removes cholesterol from the blood and is associated with a reduced risk of atherosclerosis and heart disease. However, if you have the misfortune to possess the genotype haptoglobin 2-1, the study shows that this same treatment can drastically decrease your HDL function and cause cardiovascular disease. Pharmacogenetics is a rising concern in clinical oncology, because the therapeutic window of most anticancer drugs is narrow and patients with impaired ability to detoxify drugs will undergo life-threatening toxicities. In particular, genetic deregulations affecting genes coding for DPD, UGT1A1, TPMT, CDA and Cyp2D6 are now considered as critical issues for patients treated with 5-FU/capecitabine, irinotecan, mercaptopurine/azathioprine, gemcitabine/capecitabine/AraC and tamoxifen, respectively. The decision to use pharmacogenetic techniques is influenced by the relative costs of genotyping technologies and the cost of providing a treatment to a patient with an incompatible genotype. When available, phenotype-based approaches proved their usefulness while being cost-effective. In the search for informative correlates of psychotropic drug response, pharmacogenetics has several advantages: *The genotype of an individual is essentially invariable and remains unaffected by the treatment itself. *Molecular biology techniques provide an accurate assessment of the genotype of an individual. *There has been a dramatic increase in the amount of genomic information that is available. This information provides the necessary data for comprehensive studies of individual genes and broad investigation of genome-wide variation. *The ease of accessibility to genotype information through peripheral blood or saliva sampling and advances in molecular techniques has increased the feasibility of DNA collection and genotyping in large-scale clinical trials. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Pharmacogenetics」の詳細全文を読む スポンサード リンク
|