Global variation in CYP2C8-CYP2C9 functional haplotypes

Pharmacogenomics J. 2009 Aug;9(4):283-90. doi: 10.1038/tpj.2009.10. Epub 2009 Apr 21.


We have studied the global frequency distributions of 10 single nucleotide polymorphisms (SNPs) across 132 kb of CYP2C8 and CYP2C9 in approximately 2500 individuals representing 45 populations. Five of the SNPs were in noncoding sequences; the other five involved the more common missense variants (four in CYP2C8, one in CYP2C9) that change amino acids in the gene products. One haplotype containing two CYP2C8 coding variants and one CYP2C9 coding variant reaches an average frequency of 10% in Europe; a set of haplotypes with a different CYP2C8 coding variant reaches 17% in Africa. In both cases these haplotypes are found in other regions of the world at <1%. This considerable geographic variation in haplotype frequencies impacts the interpretation of CYP2C8/CYP2C9 association studies, and has pharmacogenomic implications for drug interactions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Africa
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asia
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 CYP2C9
  • Europe
  • Gene Frequency
  • Genetics, Population
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide


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