Genetic polymorphism of cytochrome P450s and P-glycoprotein in the Finnish population.
The objective of this study was to investigate the genetic polymorphism of selected cytochrome P450 (CYP) enzymes and ABCB1 (encoding P-glycoprotein) of central importance with regard to the disposition of clinically used drugs in the Finnish population and to compare the results to pre-existing data from Caucasian populations. A random sample of 449 Finns was studied. Single nucleotide polymorphisms (SNPs) were genotyped using blood-derived genomic DNA and 5'-nuclease assays. We found that the allele frequencies of CYP1A2 SNP g.-163C>A, CYP2C8*3, CYP2C9*2, CYP2C9*3 and CYP2C19*2 were similar to those seen in other Caucasian populations. However, the allelic frequency of the variant ABCB1 SNP c.3435C>T allele was lower than previously reported. The frequency of the homozygous CYP3A5*1 expression was significantly higher than expected based on Hardy-Weinberg calculations (observed n = 8 vs. expected n = 3, P = 0.01). Other genotype frequencies corresponded to the expected values. The strong linkage between the CYP2C8*3 and the CYP2C9*2 alleles was confirmed in this study and the number of individuals with the rare haplotype CYP2C8*3*3/CYP2C9*2*2 was higher than expected. We conclude that the frequency of mutated CYP alleles in Finns were in agreement with earlier findings in Caucasian populations, but a lower frequency of the ABCB1 variant allele 3435T corresponding to that reported in Asian populations was found. The higher than expected frequency of the CYP3A5*1*1 genotype and the CYP2C8*3*3/CYP2C9*2*2 haplotype may influence the response to treatment with drugs metabolized by these enzymes.
Hilli
Johanna
J
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, 3rd floor, FIN-20520 Turku, Finland. johanna.hilli@utu.fi
Rane
Anders
A
Lundgren
Stefan
S
Bertilsson
Leif
L
Laine
Kari
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005387:Finland; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D011110:Polymorphism, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; C450259:CYP2C8 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8