Citation

Pirmohamed M. Pathology 2020; 52(Suppl 1): S16-S17.

Copyright

(Copyright © 2020, Elsevier Publishing)

DOI

10.1016/j.pathol.2020.01.089

PMID

unavailable

Abstract

Adverse drug reactions (ADRs) are a major clinical problem accounting for a great deal of morbidity, mortality and are a drain on healthcare resources. ADRs can generally be divided into on-target and off-target reactions. Both types of ADRs have a genetic predisposition, but the quantitative contribution of genetic vs non-genetic factors varies with the type of reaction, the drug implicated and the patient's clinical co-morbidities. My talk will focus on genetic factors predisposing to ADRs, and how advances over the last 20 years have led not only to discovery, but also to some genetic tests becoming incorporated into clinical practice. There are some well-known polymorphisms in genes such as Glucose-6-phosphate dehydrogenase and butyrylcholinesterase which have been known about for decades, and testing can be undertaken in healthcare systems. More recently, the role of HLA and predisposition to immune mediated adverse reactions has been particularly fertile in identifying new associations, often through genome wide technologies. Indeed, since 2001, at least 30 new HLA-ADR associations have been reported. Two of these are in clinical practice (HLA-B*57:01 for abacavir hypersensitivity, and HLA-B*15:02 for carbamazepine-induced Stevens-Johnson Syndrome). Genetic factors can also determine dose; for example, for warfarin, polymorphisms in VKORC1 and CYP2C9 account for almost 50% of the variance in individual dose requirements. Investigation of the genomic basis of ADRs is not only important for development of predictive genetic testing, but can also provide insights into the mechanisms of ADRs.

Language: en