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dc.creatorPetrović, Jelena
dc.creatorPešić, Vesna
dc.creatorLauschke, Volker M.
dc.date.accessioned2020-02-12T11:01:32Z
dc.date.available2020-02-12T11:01:32Z
dc.date.issued2020
dc.identifier.issn1018-4813
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3501
dc.description.abstractCYP2C19 and CYP2D6 are important drug-metabolizing enzymes that are involved in the metabolism of around 30% of allmedications. Importantly, the corresponding genes are highly polymorphic and these genetic differences contribute tointerindividual and interethnic differences in drug pharmacokinetics, response, and toxicity. In this study we systematicallyanalyzed the frequency distribution of clinically relevantCYP2C19andCYP2D6alleles across Europe based on data from82,791 healthy individuals extracted from 79 original publications and, for thefirst time, provide allele confidence intervalsfor the general population. We found that frequencies ofCYP2D6gene duplications showed a clear South-East to North-West gradient ranging from <1% in Sweden and Denmark to 6% in Greece and Turkey. In contrast, an inverse distributionwas observed for the loss-of-function allelesCYP2D6*4andCYP2D6*5. Similarly, frequencies of the inactiveCYP2C19*2allele were graded from North-West to South-East Europe. In important contrast to previous work we found that theincreased activity alleleCYP2C19*17was most prevalent in Central Europe (25–33%) with lower prevalence inMediterranean-South Europeans (11–24%). In summary, we provide a detailed European map of commonCYP2C19andCYP2D6variants andfind that frequencies of the most clinically relevant alleles are geographically graded reflective ofEurope’s migratory history. Thesefindings emphasize the importance of generating pharmacogenomic data sets with highspatial resolution to improve precision public health across Europe.en
dc.publisherSpringer Nature
dc.relationSwedish Research Council [grant agreement numbers:2016–01153 and 2016–01154]
dc.relationuropean Union’s Horizon2020 research and innovation program U-PGx [grant agreementnumber 668353]
dc.rightsopenAccess
dc.sourceEuropean Journal of Human Genetics
dc.subjectcytochrome P450 2C19
dc.subjectcytochrome P450 2D6
dc.subjectgene duplication
dc.subjectgene frequency
dc.subjecthuman
dc.titleFrequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europeen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractПетровић, Јелена; Пешић, Весна; Лаусцхке, Волкер М.;
dc.citation.volume28
dc.citation.issue1
dc.citation.spage88
dc.citation.epage94
dc.citation.rankM21~
dc.identifier.wos000502538900012
dc.identifier.doi10.1038/s41431-019-0480-8
dc.identifier.scopus2-s2.0-85069909977
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/7485/Frequencies_of_clinicall_pub_2020.pdf
dc.type.versionpublishedVersion


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