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High Frequency of CYP 2D6 Ultrarapid Metabolizer Genotype in the Finnish Population
Author(s) -
Pietarinen Paavo,
Tornio Aleksi,
Niemi Mikko
Publication year - 2016
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12590
Subject(s) - cyp2d6 , genotype , genotyping , pharmacogenetics , population , taqman , genetics , biology , confidence interval , allele frequency , medicine , polymerase chain reaction , gene , environmental health
Abstract CYP 2D6 participates in the biotransformation of many commonly used drugs. Large genetic variability in CYP 2D6 results in a wide interindividual variability in the response to CYP 2D6 substrate drugs. Previous studies have assessed the phenotype and genotype distributions of CYP 2D6 in relatively small Finnish population samples. The aim of our study was to investigate the frequencies of CYP 2D6 genotypes in a larger Finnish population cohort of 857 healthy volunteers. The volunteers were genotyped for 10 CYP 2D6 genetic variants ( *2 , *3 , *4 , *5 , *6 , *9 , *10 , *17 , *39 , *41 ) and copy number variation performed with TaqMan genotyping assays and copy number assay targeting exon 9. CYP 2D6 phenotypes were inferred from the genotype data with the classical and activity score methods. According to the classical method, a large majority of the study cases were extensive metabolizers ( EM ; 87.3%; 95% confidence interval 84.9–89.3) and the second largest group was ultrarapid metabolizers ( UM ; 7.2%; 5.7–9.2%). Intermediate ( IM ) and poor metabolizers ( PM ) were in clear minority (3.0%; 2.1–4.4% and 2.3%; 1.5–3.6%, respectively). The activity score method yielded similar phenotype predictions. These results show that the frequency of UM genotype is higher and that of PM and IM genotype is lower in the Finnish population than in other North European populations. Accordingly, CYP 2D6 genetic profile of the Finnish population differs from its geographically close neighbours, which has implications for the effective and safe use of drugs metabolized by CYP 2D6.