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. 2010 Dec;66(12):1199-205. doi: 10.1007/s00228-010-0864-8. Epub 2010 Jul 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 CYP2C9
  • Denmark
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium*
  • Norway

Substances

  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C8