title: Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population.
abstract: OBJECTIVE
  The purpose of the study was to study the distribution of poor and extensive metabolizers of CYP2C19 and CYP2D6 and to genotype for CYP2C8 and CYP2C9 among 312 randomly selected Faroese.
  
  
  RESULTS
  The participants were phenotyped for CYP2D6 with the use of sparteine. The distribution of the sparteine metabolic ratio (sparteine/didehydrosparteines) was bimodal, and 14.5% (n=44; 95% CI: 10.7--18.9%) of the subjects were phenotyped as poor metabolizers. The frequency of poor metabolizers was higher (P=0.0002; chi(2) test) among the Faroese than in other European populations (7.4%). Genotype analyses for the CYP2D6*3, *4, *6 and *9 alleles were performed using real-time polymerase chain reaction (PCR) (TaqMan, Foster City, CA, USA), and we found 14.6% (n=45) (95% CI: 10.8--19.0%) with deficient CYP2D6 genes (*3/*4, *4/*4, *4/*6, *6/*6) in the Faroese population. The subjects were phenotyped for CYP2C19 with the use of mephenytoin and 10 subjects, i.e., 3.2% (95% CI: 1.6--5.9%) were phenotyped as poor metabolizers. Genotype analysis for the CYP2C19*2 and *3 alleles was performed by means of PCR analysis, and 2.9% (n=9) (95% CI: 1.3-5.4%) of the Faroese were found to have a deficient CYP2C19 gene all explained by the CYP2C19*2/*2 genotype. The allele frequencies of the CYP2C9*2 and CYP2C9*3 alleles were 8.8% (95% CI: 6.7--11.4%) and 5.3% (95% CI: 3.7--7.4%), respectively, while the CYP2C8*3 allele frequency was 6.9% (95% CI: 5.0--9.2%). Real-time PCR (TaqMan) was used for both CYP2C9 and CYP2C8 genotype analyses.
  
  
  CONCLUSIONS
  The frequency of CYP2D6 poor metabolizers is twofold higher among the Faroese population than other Caucasians, while the frequencies of Faroese subjects with decreased CYP2C19, CYP2C8 and CYP2C9 enzyme activity are the same as seen in other Caucasian populations. A possible consequence might be a higher incidence of side effects among Faroese patients taking pharmaceuticals that are CYP2D6 substrates.
authors: Clinical Pharmacology, Faculty of Health Sciences, Institute of Public Health, University of Southern Denmark, Winslovparken 19, 5000 Odense C, Denmark. jhalling@health.sdu.dk
authors: Jónrit
authors: J
authors: Halling
authors: Maria S
authors: MS
authors: Petersen
authors: Per
authors: P
authors: Damkier
authors: Flemming
authors: F
authors: Nielsen
authors: Philippe
authors: P
authors: Grandjean
authors: Pál
authors: P
authors: Weihe
authors: Stefan
authors: S
authors: Lundgren
authors: Mia Sandberg
authors: MS
authors: Lundblad
authors: Kim
authors: K
authors: Brøsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D064420:Drug-Related Side Effects and Adverse Reactions; D005828:Genetics, Population; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C450259:CYP2C8 protein, human; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D019389:Cytochrome P-450 CYP2D6