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Licensed Unlicensed Requires Authentication Published by De Gruyter January 23, 2015

Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland

  • Kim Brosen EMAIL logo


Denmark, the Faroe Islands and Greenland are three population-wise small countries on the northern part of the Northern Hemisphere, and studies carried out here on the genetic control over drug metabolism via cytochrome P450 have led to several important discoveries. Thus, CYP2D6 catalyzes the 2-hydroxylation, and CYP2C19 in part catalyzes the N-demethylation of imipramine. The phenomenon of phenocopy with regard to CYP2D6 was first described when Danish patients changed phenotype from extensive to poor metabolizers during treatment with quinidine. It was a Danish extensive metabolizer patient that became a poor metabolizer during paroxetine treatment, and this was due to the potent inhibition of CYP2D6 by paroxetine, which is also is metabolized by this enzyme. Fluoxetine and norfluoxetine are also potent inhibitors of CYP2D6, and fluvoxamine is a potent inhibitor of both CYP1A2 and CYP2C19. The bioactivation of proguanil to cycloguanil is impaired in CYP2C19 poor metabolizers. The O-demethylation of codeine and tramadol to their respective my-opioid active metabolites, morphine and (+)-O-desmethyltramadol was markedly impaired in CYP2D6 poor metabolizers compared to extensive metabolizers, and this impairs the hypoalgesic effect of the two drugs in the poor metabolizers. The frequency of CYP2D6 poor metabolizers is 2%–3% in Greenlanders and nearly 15% in the Faroese population. The frequency of CYP2C19 poor metabolizers in East Greenlanders is approximately 10%. A study in Danish mono and dizygotic twins showed that the non-polymorphic 3-N-demethylation of caffeine catalyzed by CYP1A2 is subject to approximately 70% genetic control.

Corresponding author: Kim Brosen, Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsløws Vej 19, 5000 Odense C, Denmark, Phone: +45 6550 3751, Mobile: +45 2015 3751, E-mail:


Karin Kramer Nielsen, Birgitte Buur Rasmussen, Jonrit Halling, Maria Skaalum Pedersen, Stine T. Zwisler, Lars F. Gram, Søren H. Sindrup, Troels Bergmann, Tore Bjerregaard Stage and Rasmus S. Pedersen have read the manuscripts and made valuable comments.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


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Received: 2014-10-8
Accepted: 2014-12-9
Published Online: 2015-1-23
Published in Print: 2015-9-1

©2015 by De Gruyter

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