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Pharmacogenetics and human genetic polymorphisms

Lookup NU author(s): Professor Ann Daly

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Abstract

The term pharmacogenetics was first used in the late 1950s and can be defined as the study of genetic factors affecting drug response. Prior to formal use of this term, there was already clinical data available in relation to variable patient responses to the drugs isoniazid, primaquine and succinylcholine. The subject area developed rapidly, particularly with regard to genetic factors affecting, drug disposition. There is now comprehensive understanding of the molecular basis for variable drug metabolism by the cytochromes P450 and also for variable glucuronidation. acetylation and methylation of certain drugs. Some of this knowledge has already been translated to the clinic. The molecular basis of variation in drug targets, such as receptors and enzymes, is generally less well understood, although there is consistent evidence that polymorphisms in the genes encoding the beta-adrenereic receptors and the enzyme vitamin K epoxide reductase is of clinical importance. The genetic basis of rare idiosyncratic adverse drug reactions had also been examined. Susceptibility to reactions affecting skin and liver appears to be determined in part by the HLA (human leucocyte antigen) genotype, whereas reactions affecting the heart and muscle may be determined by polymorphisms in genes encoding ion channels and transporters respectively. Genome-wide association studies are increasingly being used to study drug response and susceptibility to adverse drug reactions, resulting in identification of some novel pharmacogenetic associations.


Publication metadata

Author(s): Daly AK

Publication type: Review

Publication status: Published

Journal: Biochemical Journal

Year: 2010

Volume: 429

Pages: 435-449

Print publication date: 01/08/2010

ISSN (print): 0264-6021

ISSN (electronic): 1470-8728

URL: http://dx.doi.org/10.1042/BJ20100522

DOI: 10.1042/BJ20100522


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