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Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To determine the distribution of clinically important CYP2C genotypes and allele frequencies in healthy Nordic populations with special focus on linkage disequilibrium.

Methods

A total of 896 healthy subjects from three Nordic populations (Danish, Faroese, and Norwegian) were genotyped for five frequent and clinically important CYP2C allelic variants: the defective CYP2C8*3, CYP2C9*2, CYP2C9*3, and CYP2C19*2 alleles, and the CYP2C19*17 allele that causes rapid drug metabolism. Linkage disequilibrium was evaluated and CYP2C haplotypes were inferred in the entire population.

Results

Ten CYP2C haplotypes were inferred, the most frequent of which (49%) was the CYP2C wildtype haplotype carrying CYP2C8*1, CYP2C9*1, and CYP2C19*1. The second most frequent haplotype (19%) is composed of CYP2C19*17, CYP2C8*1, and CYP2C9*1. This predicted haplotype accounts for 99.7% of the CYP2C19*17 alleles found in the 896 subjects.

Conclusion

CYP2C19*17 is a frequent genetic variant in Nordic populations that exists in strong linkage disequilibrium with wildtype CYP2C8*1 and CYP2C9*1 alleles, which effectively makes it a determinant for a haplotype exhibiting an efficient CYP2C substrate metabolism.

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Acknowledgements

This research was supported in part by grants from The Swedish Research Council, Torsten and Ragnar Söderbergs Stiftelser, Karolinska Institutet, The Danish Research Council for Health and Disease, and The Lundbeck Foundation. We thank Pernille Jordan for analytical expertise.

Author information

Authors and Affiliations

  1. Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark

    Rasmus S. Pedersen, Charlotte Brasch-Andersen, Troels K. Bergmann, Jónrit Halling, Maria S. Petersen & Kim Brøsen

  2. Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Rasmus S. Pedersen, Sarah C. Sim & Magnus Ingelman-Sundberg

  3. Department of Occupational Medicines and Public Health, The Faroese Hospital System, Tòrshavn, Faroe Islands

    Jónrit Halling, Maria S. Petersen & Pál Weihe

  4. Department of Genetics, Institute of Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway

    Hege Edvardsen & Vessela N. Kristensen

  5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Hege Edvardsen & Vessela N. Kristensen

  6. EpiGen, Institute for Clinical Medicine, Akershus University Hospital, Oslo, Norway

    Vessela N. Kristensen

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  1. Rasmus S. Pedersen
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  2. Charlotte Brasch-Andersen
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Correspondence to Rasmus S. Pedersen.

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Pedersen, R.S., Brasch-Andersen, C., Sim, S.C. et al. Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations. Eur J Clin Pharmacol 66, 1199–1205 (2010). https://doi.org/10.1007/s00228-010-0864-8

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