Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland
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-hyd...
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ftsydanskunivpub:oai:sdu.dk:publications/42c7c107-4949-4758-8346-bbeede870914 2023-05-15T16:10:42+02:00 Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland Brøsen, Kim 2015-09 https://portal.findresearcher.sdu.dk/da/publications/42c7c107-4949-4758-8346-bbeede870914 https://doi.org/10.1515/dmdi-2014-0029 eng eng info:eu-repo/semantics/restrictedAccess Brøsen , K 2015 , ' Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland ' , Drug Metabolism and Personalized Medicine , vol. 30 , no. 3 , pp. 147-163 . https://doi.org/10.1515/dmdi-2014-0029 Atlantic Islands Biotransformation Cytochrome P-450 Enzyme System/genetics Denmark Greenland Humans Inuits Oxidation-Reduction Pharmacokinetics Polymorphism Genetic article 2015 ftsydanskunivpub https://doi.org/10.1515/dmdi-2014-0029 2022-08-14T09:14:59Z 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. Article in Journal/Newspaper Faroe Islands Greenland greenlander* inuits University of Southern Denmark Research Portal Faroe Islands Greenland Drug Metabolism and Personalized Therapy 30 3 |
institution |
Open Polar |
collection |
University of Southern Denmark Research Portal |
op_collection_id |
ftsydanskunivpub |
language |
English |
topic |
Atlantic Islands Biotransformation Cytochrome P-450 Enzyme System/genetics Denmark Greenland Humans Inuits Oxidation-Reduction Pharmacokinetics Polymorphism Genetic |
spellingShingle |
Atlantic Islands Biotransformation Cytochrome P-450 Enzyme System/genetics Denmark Greenland Humans Inuits Oxidation-Reduction Pharmacokinetics Polymorphism Genetic Brøsen, Kim Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
topic_facet |
Atlantic Islands Biotransformation Cytochrome P-450 Enzyme System/genetics Denmark Greenland Humans Inuits Oxidation-Reduction Pharmacokinetics Polymorphism Genetic |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Brøsen, Kim |
author_facet |
Brøsen, Kim |
author_sort |
Brøsen, Kim |
title |
Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
title_short |
Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
title_full |
Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
title_fullStr |
Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
title_full_unstemmed |
Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland |
title_sort |
pharmacogenetics of drug oxidation via cytochrome p450 (cyp) in the populations of denmark, faroe islands and greenland |
publishDate |
2015 |
url |
https://portal.findresearcher.sdu.dk/da/publications/42c7c107-4949-4758-8346-bbeede870914 https://doi.org/10.1515/dmdi-2014-0029 |
geographic |
Faroe Islands Greenland |
geographic_facet |
Faroe Islands Greenland |
genre |
Faroe Islands Greenland greenlander* inuits |
genre_facet |
Faroe Islands Greenland greenlander* inuits |
op_source |
Brøsen , K 2015 , ' Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland ' , Drug Metabolism and Personalized Medicine , vol. 30 , no. 3 , pp. 147-163 . https://doi.org/10.1515/dmdi-2014-0029 |
op_rights |
info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1515/dmdi-2014-0029 |
container_title |
Drug Metabolism and Personalized Therapy |
container_volume |
30 |
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3 |
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1765995860515094528 |