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

  • Pharmacogenetics
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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: 3.7–7.4%), 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.

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.

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Acknowledgements

This study was supported by “Apotekerfonden af 1991”, and by grants from the Swedish Science Council, Medicine (00496). The assistance of the employees at the Department of Occupational and Public Health in Tórshavn, Faroe Islands, is highly appreciated. 2,3-Didehydrosparteine and 5,6-didehydrosparteine were kindly donated by Michael Eichelbaum from Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology in Stuttgart, Germany.

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Authors and Affiliations

  1. Clinical Pharmacology, Faculty of Health Sciences, Institute of Public Health, University of Southern Denmark, Winslovparken 19, 5000, Odense C, Denmark

    Jónrit Halling, Flemming Nielsen & Kim Brøsen

  2. Environmental Medicine, Institute of Public Health, University of Southern Denmark, Winslovparken 17, 5000, Odense C, Denmark

    Maria S. Petersen, Flemming Nielsen & Philippe Grandjean

  3. Department KKA, Clinical Pharmacology, Odense University Hospital, Odense, Denmark

    Per Damkier

  4. Department of Occupational and Public Health, The Faroese Hospital System, Sigmundargota 5, 100, Tórshavn, Faroe Islands

    Pál Weihe

  5. Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Stefan Lundgren & Mia Sandberg Lundblad

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  1. Jónrit Halling
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Correspondence to Jónrit Halling.

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Halling, J., Petersen, M.S., Damkier, P. et al. Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population. Eur J Clin Pharmacol 61, 491–497 (2005). https://doi.org/10.1007/s00228-005-0938-1

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  • DOI: https://doi.org/10.1007/s00228-005-0938-1

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