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Clinical applications of pharmacogenetics

Tate, SK; (2007) Clinical applications of pharmacogenetics. Doctoral thesis, UCL (University College London). Green open access

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Abstract

The field of pharmacogenetics has grown rapidly over the last few years yet, with a couple of exceptions, pharmacogenetic diagnostics are not yet used in a clinical setting. Progress in the field is discussed and the current state of pharmacogenetic research is assessed in a literature review. This thesis describes studies to investigate the pharmacogenetics of the anti-epileptic drugs phenytoin, carbamazepine and levetiracetam, using data obtained from the routine clinical use of these drugs, and the pharmacogenetics of the beta-blocker bucindolol in a clinical trial setting. Evidence is presented of a common polymorphism in the SCN1A gene that is associated with the clinical use (dosing) of both phenytoin and carbamazepine. Preliminary results are also presented concerning genetic variation in the SV2A and SV2C genes which may influence response to levetiracetam. For this study genetic variation was represented using the tagging SNP method applied to HapMap data. Genetic variation in ADRB2 may influence response to bucindolol yet the results are not conclusive. More importantly however, they do provide an illustration of how differences in polymorphism frequencies among populations could account for average differences in drug response among populations. It is also shown that there are substantial genetic differences within self-identified racial groups within the context of a clinical trial. The implications of pharmacogenetics for different racial or ethnic groups are discussed in a separate chapter. In conclusion, common variation in obvious candidate genes does influence drug response, however, rigorous clinical study is required before the use of pharmacogenetic variants to guide choice or dose of drugs becomes part of clinical practice.

Type: Thesis (Doctoral)
Title: Clinical applications of pharmacogenetics
Identifier: PQ ETD:593462
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: http://discovery.ucl.ac.uk/id/eprint/1446133
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