TY  - JOUR
AU  - Petrović, Jelena
AU  - Pešić, Vesna
AU  - Lauschke, Volker M.
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3501
AB  - CYP2C19 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.
PB  - Springer Nature
T2  - European Journal of Human Genetics
T1  - Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe
VL  - 28
IS  - 1
SP  - 88
EP  - 94
DO  - 10.1038/s41431-019-0480-8
ER  - 

@article{
author = "Petrović, Jelena and Pešić, Vesna and Lauschke, Volker M.",
year = "2020",
abstract = "CYP2C19 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.",
publisher = "Springer Nature",
journal = "European Journal of Human Genetics",
title = "Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe",
volume = "28",
number = "1",
pages = "88-94",
doi = "10.1038/s41431-019-0480-8"
}

Petrović, J., Pešić, V.,& Lauschke, V. M.. (2020). Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. in European Journal of Human Genetics
Springer Nature., 28(1), 88-94.
https://doi.org/10.1038/s41431-019-0480-8

Petrović J, Pešić V, Lauschke VM. Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. in European Journal of Human Genetics. 2020;28(1):88-94.
doi:10.1038/s41431-019-0480-8 .

Petrović, Jelena, Pešić, Vesna, Lauschke, Volker M., "Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe" in European Journal of Human Genetics, 28, no. 1 (2020):88-94,
https://doi.org/10.1038/s41431-019-0480-8 . .