Pharmacogenetics: Difference between revisions
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'''Pharmacogenetics''' is the study of inherited [[genetics|genetic]] differences in drug [[metabolic pathway]]s (and other pharmacological principles, like enzymes, messengers and receptors) which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.<ref name="Klotz-2007">{{Cite journal | last1 = Klotz | first1 = U. | title = The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. | journal = Clin Pharmacokinet | volume = 46 | issue = 4 | pages = 271–9 | month = | year = 2007 | doi = 10.2165/00003088-200746040-00001| pmid = 17375979 }}</ref> 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 behaviour through a systematic examination of genes, gene products, and inter- and intra-individual variation in gene expression and function.<ref>{{cite web| title= Center for Pharmacogenomics and Individualized Therapy| url=https://pharmacy.unc.edu/research/centers/cpit/| accessdate=2017-03-08}}</ref> |
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In oncology, ''pharmacogenetics'' historically is the study of [[germline mutation]]s (e.g., [[single-nucleotide polymorphism]]s affecting genes coding for liver enzymes responsible for drug deposition and [[pharmacokinetics]]), whereas ''pharmacogenomics'' refers to [[mutation|somatic mutations]] in [[cancer|tumoral]] DNA leading to alteration in drug response (e.g., [[KRAS]] mutations in patients treated with [[epidermal growth factor receptor|anti-Her1]] [[biologic medical product|biologics]]).<ref name="pmid10866212">{{cite journal | author = Roses AD | title = Pharmacogenetics and the practice of medicine | journal = Nature | volume = 405 | issue = 6788 | pages = 857–65 |date=June 2000 | pmid = 10866212 | doi = 10.1038/35015728 }}</ref> Pharmacogenetics is believed to account for inter-ethnic differences (e.g., between patients of Asian, Caucasian and African descent) in adverse events and efficacy profiles of many widely used drugs in cancer chemotherapy.<ref>{{cite journal | vauthors = Syn NL, Yong WP, Lee SC, Goh BC | title = Genetic factors affecting drug disposition in Asian cancer patients | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 11 | issue = 12 | pages = 1879–92 | date = 2015-01-01 | pmid = 26548636 | doi = 10.1517/17425255.2015.1108964 }}</ref> |
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==History== |
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The first observations of genetic variation in drug response date from the 1950s, involving the muscle relaxant [[suxamethonium chloride]], and drugs metabolized by [[N-acetyltransferase]]. One in 3500 [[Caucasian race|Caucasians]] has less efficient variant of the [[enzyme]] ([[butyrylcholinesterase]]) that [[metabolize]]s suxamethonium chloride.<ref name="pmid16968950">{{cite journal |vauthors=Gardiner SJ, Begg EJ | title = Pharmacogenetics, drug-metabolizing enzymes, and clinical practice | journal = Pharmacol. Rev. | volume = 58 | issue = 3 | pages = 521–90 |date=September 2006 | pmid = 16968950 | doi = 10.1124/pr.58.3.6 | url = | issn = }}</ref> As a consequence, the drug’s effect is prolonged, with slower recovery from surgical paralysis. Variation in the [[N-acetyltransferase]] gene divides people into "slow acetylators" and "fast acetylators", with very different [[Mean lifetime|half-lives]] and [[blood concentration]]s of such important drugs as [[isoniazid]] (antituberculosis) and [[procainamide]] (antiarrhythmic). As part of the inborn system for clearing the body of [[xenobiotic]]s, the [[cytochrome P450 oxidase]]s (CYPs) are heavily involved in [[drug metabolism]], and genetic variations in CYPs affect large populations. One member of the CYP superfamily, [[CYP2D6]], now has over 75 known allelic variations, some of which lead to no activity, and some to enhanced activity. An estimated 29% of people in parts of [[East Africa]] may have multiple copies of the gene, and will therefore not be adequately treated with standard doses of drugs such as the painkiller [[codeine]] (which is activated by the enzyme). The first study using Genome-wide association studies (GWAS) linked age-related macular degeneration (AMD) with a SNP located on chromosome 1 that increased one’s risk of AMD. AMD is the most common cause of blindness, affecting more than seven million Americans. Until this study in 2005, we only knew about the inflammation of the retinal tissue causing AMD, not the genes responsible.<ref name="isbn0-465-02550-1">{{cite book|title=The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care|publisher=Basic Books|year=2012|isbn=978-0-465-02550-3|location=New York|pages=|doi=|oclc=}}</ref> |
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==See also== |
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* [[Chemogenomics]] |
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* [[Personalized medicine]] |
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* [[Pharmacovigilance]] |
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* [[Structural genomics]] |
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* [[Toxicogenomics]] |
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==References== |
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{{Reflist|30em}} |
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== Further reading == |
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{{refbegin|2}} |
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* {{cite journal | author = Abbott A | title = With your genes? Take one of these, three times a day | journal = Nature | volume = 425 | issue = 6960 | pages = 760–2 |date=October 2003 | pmid = 14574377 | doi = 10.1038/425760a | url = | issn = }} |
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* {{cite journal |vauthors=Evans WE, McLeod HL | title = Pharmacogenomics – drug disposition, drug targets, and side effects | journal = N. Engl. J. Med. | volume = 348 | issue = 6 | pages = 538–49 |date=February 2003 | pmid = 12571262 | doi = 10.1056/NEJMra020526 | url = | issn = }} |
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* {{cite journal |vauthors=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W | title = Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review | journal = JAMA | volume = 286 | issue = 18 | pages = 2270–9 |date=November 2001 | pmid = 11710893 | doi = 10.1001/jama.286.18.2270| url = | issn = }} |
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* {{cite journal | vauthors = Weinshilboum R | title = Inheritance and drug response | journal = The New England Journal of Medicine | volume = 348 | issue = 6 | pages = 529–37 | date = February 2003 | pmid = 12571261 | doi = 10.1056/NEJMra020021 }} |
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{{Refend}} |
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==External links== |
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*[http://www.ornl.gov/sci/techresources/Human_Genome/medicine/pharma.shtml Pharmacogenomics: Medicine and the new genetics] from the Human Genome Project |
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* [https://www.springer.com/humana+press/pharmacology+and+toxicology/book/978-1-58829-887-4 ''Pharmacogenomics in Drug Discovery and Development''], a book on pharmacogenomics , diseases, personalized medicine, and therapeutics |
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{{Pharmacology}} |
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{{Genomics}} |
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[[Category:Pharmacology]] |
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[[Category:Pharmacy]] |
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Revision as of 20:34, 17 June 2019
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