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

Rasmus S. Pedersen, Charlotte Brasch-Andersen, Sarah C. Sim, Troels K. Bergmann, J Halling, MS Petersen, P Weihe, Helge Edvardsen, Vessela N. Kristensen, Kim Brosen, Magnus Ingelman-Sundberg

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

To determine the distribution of clinically important CYP2C genotypes and allele frequencies in healthy Nordic populations with special focus on linkage disequilibrium. 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. 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. 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.
Original languageEnglish
Pages (from-to)1199-1205
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Volume66
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • CYP2C haplotypes
  • CYP2C19*17
  • Linkage disequilibrium
  • Allele frequencies
  • HUMAN DRUG-METABOLISM
  • GENETIC POLYMORPHISMS
  • CLINICAL-RELEVANCE
  • CYTOCHROME P4502C9
  • SUBFAMILY
  • ESCITALOPRAM
  • ASSOCIATION
  • OMEPRAZOLE
  • INHIBITORS
  • VARIANT

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