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European Journal of Clinical Pharmacology

, Volume 66, Issue 12, pp 1199–1205 | Cite as

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

  • Rasmus S. PedersenEmail author
  • Charlotte Brasch-Andersen
  • Sarah C. Sim
  • Troels K. Bergmann
  • Jónrit Halling
  • Maria S. Petersen
  • Pál Weihe
  • Hege Edvardsen
  • Vessela N. Kristensen
  • Kim Brøsen
  • Magnus Ingelman-Sundberg
Pharmacogenetics

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.

Keywords

CYP2C haplotypes CYP2C19*17 Linkage disequilibrium Allele frequencies 

Notes

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.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Rasmus S. Pedersen
    • 1
    • 2
    Email author
  • Charlotte Brasch-Andersen
    • 1
  • Sarah C. Sim
    • 2
  • Troels K. Bergmann
    • 1
  • Jónrit Halling
    • 1
    • 3
  • Maria S. Petersen
    • 1
    • 3
  • Pál Weihe
    • 3
  • Hege Edvardsen
    • 4
    • 5
  • Vessela N. Kristensen
    • 4
    • 5
    • 6
  • Kim Brøsen
    • 1
  • Magnus Ingelman-Sundberg
    • 2
  1. 1.Institute of Public Health, Clinical PharmacologyUniversity of Southern DenmarkOdenseDenmark
  2. 2.Section of Pharmacogenetics, Department of Physiology and PharmacologyKarolinska InstitutetStockholmSweden
  3. 3.Department of Occupational Medicines and Public HealthThe Faroese Hospital SystemTòrshavnFaroe Islands
  4. 4.Department of Genetics, Institute of Cancer ResearchOslo University Hospital RadiumhospitaletOsloNorway
  5. 5.Institute of Clinical MedicineUniversity of OsloOsloNorway
  6. 6.EpiGen, Institute for Clinical MedicineAkershus University HospitalOsloNorway

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