European Journal of Clinical Pharmacology

, Volume 61, Issue 7, pp 491–497

Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population

  • Jónrit Halling
  • Maria S. Petersen
  • Per Damkier
  • Flemming Nielsen
  • Philippe Grandjean
  • Pál Weihe
  • Stefan Lundgren
  • Mia Sandberg Lundblad
  • Kim Brøsen
Pharmacogenetics

DOI: 10.1007/s00228-005-0938-1

Cite this article as:
Halling, J., Petersen, M.S., Damkier, P. et al. Eur J Clin Pharmacol (2005) 61: 491. doi:10.1007/s00228-005-0938-1

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.

Methods and 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; χ2 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: 3.77.4%), 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.

Conclusion

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.

Keywords

CYP2D6CYP2C19CYP2C8CYP2C9Faroe IslandsPolymorphism

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jónrit Halling
    • 1
  • Maria S. Petersen
    • 2
  • Per Damkier
    • 3
  • Flemming Nielsen
    • 1
    • 2
  • Philippe Grandjean
    • 2
  • Pál Weihe
    • 4
  • Stefan Lundgren
    • 5
  • Mia Sandberg Lundblad
    • 5
  • Kim Brøsen
    • 1
  1. 1.Clinical Pharmacology, Faculty of Health Sciences, Institute of Public HealthUniversity of Southern DenmarkOdense CDenmark
  2. 2.Environmental Medicine, Institute of Public HealthUniversity of Southern DenmarkOdense CDenmark
  3. 3.Department KKA, Clinical PharmacologyOdense University HospitalOdenseDenmark
  4. 4.Department of Occupational and Public HealthThe Faroese Hospital SystemTórshavnFaroe Islands
  5. 5.Division of Clinical PharmacologyKarolinska University Hospital HuddingeStockholmSweden