title: Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory.
abstract: OBJECTIVE
  We sought to determine the genotype frequencies for cytochrome p450 enzyme 2C19 variant alleles both in the US pan-ethnic population and various US ethnic groups and to establish the frequency of clinically actionable genotypes.
  
  
  METHODS
  Analytical results were obtained from 1,396 consecutive samples submitted for cytochrome p450 enzyme 2C19 genotyping tests and stored in a proprietary database. This database was queried and genotypes and predicted phenotypes established. Anonymized samples were obtained from specimens submitted for cystic fibrosis genotyping that contained ethnicity information. Samples from 357, 149, and 346 individuals self-identified as white, African American, and Hispanic, respectively, were analyzed. In addition, 342 anonymized samples submitted for Ashkenazi Jewish panel testing were analyzed.
  
  
  RESULTS
  Significant ethnic differences were observed in the frequencies of the *17 ultrarapid allele among the various groups studied. In the pan-ethnic population, 3.8% of tested patients were classified as ultrarapid metabolizers, 24% as extensive metabolizers heterozygous for a *17 ultrarapid allele, 27% as intermediate metabolizers, and 3.5% as poor metabolizers. Using stringent criteria, 7.3% of individuals would have clinically actionable genotypes. In addition, we detected two individuals with a haplotype of *2/*17 and a single individual with a haplotype of *4/*17 indicating that the *17 hypermetabolic allele can occur on a *1, *2, or *4 background.
authors.affiliation: Genetic Testing Center, Nichols Institute Quest Diagnostics, San Juan Capistrano, California, USA. Charles.M.Strom@QuestDiagnostics.com
authors.forename: Charles M
authors.initials: CM
authors.lastname: Strom
authors.forename: Dana
authors.initials: D
authors.lastname: Goos
authors.forename: Beryl
authors.initials: B
authors.lastname: Crossley
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Arlene
authors.initials: A
authors.lastname: Buller-Burkle
authors.forename: Michael
authors.initials: M
authors.lastname: Jarvis
authors.forename: Franklin
authors.initials: F
authors.lastname: Quan
authors.forename: Mei
authors.initials: M
authors.lastname: Peng
authors.forename: Weimin
authors.initials: W
authors.lastname: Sun
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D019411:Clinical Laboratory Techniques; D065731:Cytochrome P-450 CYP2C19; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010641:Phenotype; D014481:United States
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19