Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes

Pharmacogenomics J. 2013 Aug;13(4):369-77. doi: 10.1038/tpj.2012.10. Epub 2012 Apr 10.

Abstract

To determine CYP2C19 and CYP2C8 allele frequencies, 28 coding and/or functional variants were genotyped in 1250 African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish (AJ) individuals. The combined CYP2C19 variant allele frequencies ranged from ∼0.30 to 0.41; however, the CYP2C8 frequencies were much lower (∼0.04-0.13). After incorporating previously reported CYP2C9 genotyping results from these populations (36 total CYP2C variants), 16 multi-ethnic CYP2C haplotypes were inferred with frequencies >0.5%. Notably, the 2C19*17-2C9*1-2C8*2 haplotype was identified among African-Americans (8%) and Hispanics (2%), indicating that CYP2C19*17 does not always tag a CYP2C haplotype that encodes efficient CYP2C-substrate metabolism. The 2C19*1-2C9*2-2C8*3 haplotype was identified in all populations except African-Americans and additional novel haplotypes were identified in selected populations (for example, 2C19*2-2C9*1-2C8*4 and 2C19*4B-2C9*1-2C8*1), together indicating that both CYP2C19*17 and *2 can be linked with other CYP2C loss-of-function alleles. These results have important implications for pharmacogenomic association studies involving the CYP2C locus and are clinically relevant when administering CYP2C-substrate medications.

Publication types

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

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asians / genetics
  • Blacks / genetics
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C8
  • Gene Frequency*
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Whites / genetics

Substances

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