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Review

A Review of the Important Role of CYP2D6 in Pharmacogenomics

1
Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool L69 3BX, UK
2
MC Diagnostics, St Asaph Business Park, Saint Asaph LL17 0LJ, UK
*
Author to whom correspondence should be addressed.
Received: 26 September 2020 / Revised: 25 October 2020 / Accepted: 28 October 2020 / Published: 30 October 2020
Cytochrome P450 2D6 (CYP2D6) is a critical pharmacogene involved in the metabolism of ~20% of commonly used drugs across a broad spectrum of medical disciplines including psychiatry, pain management, oncology and cardiology. Nevertheless, CYP2D6 is highly polymorphic with single-nucleotide polymorphisms, small insertions/deletions and larger structural variants including multiplications, deletions, tandem arrangements, and hybridisations with non-functional CYP2D7 pseudogenes. The frequency of these variants differs across populations, and they significantly influence the drug-metabolising enzymatic function of CYP2D6. Importantly, altered CYP2D6 function has been associated with both adverse drug reactions and reduced drug efficacy, and there is growing recognition of the clinical and economic burdens associated with suboptimal drug utilisation. To date, pharmacogenomic clinical guidelines for at least 48 CYP2D6-substrate drugs have been developed by prominent pharmacogenomics societies, which contain therapeutic recommendations based on CYP2D6-predicted categories of metaboliser phenotype. Novel algorithms to interpret CYP2D6 function from sequencing data that consider structural variants, and machine learning approaches to characterise the functional impact of novel variants, are being developed. However, CYP2D6 genotyping is yet to be implemented broadly into clinical practice, and so further effort and initiatives are required to overcome the implementation challenges and deliver the potential benefits to the bedside. View Full-Text
Keywords: CYP2D6; pharmacogenomics; drug metabolism; population variability; structural variation CYP2D6; pharmacogenomics; drug metabolism; population variability; structural variation
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MDPI and ACS Style

Taylor, C.; Crosby, I.; Yip, V.; Maguire, P.; Pirmohamed, M.; Turner, R.M. A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes 2020, 11, 1295. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111295

AMA Style

Taylor C, Crosby I, Yip V, Maguire P, Pirmohamed M, Turner RM. A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes. 2020; 11(11):1295. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111295

Chicago/Turabian Style

Taylor, Christopher, Ian Crosby, Vincent Yip, Peter Maguire, Munir Pirmohamed, and Richard M. Turner 2020. "A Review of the Important Role of CYP2D6 in Pharmacogenomics" Genes 11, no. 11: 1295. https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111295

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