title: DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping.
abstract: BACKGROUND
  An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology.
  
  
  METHODS
  A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype.
  
  
  RESULTS
  In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%).
  
  
  CONCLUSIONS
  We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.
authors.affiliation: Mental Health Research Center, Eastern State Hospital, Lexington, KY 40508, USA. jdeleon@uky.edu
authors.forename: Jose
authors.initials: J
authors.lastname: de Leon
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Susce
authors.forename: Maria
authors.initials: M
authors.lastname: Johnson
authors.forename: Mike
authors.initials: M
authors.lastname: Hardin
authors.forename: Lorraine
authors.initials: L
authors.lastname: Maw
authors.forename: Alison
authors.initials: A
authors.lastname: Shao
authors.forename: Antonette C P
authors.initials: AC
authors.lastname: Allen
authors.forename: Francis A
authors.initials: FA
authors.lastname: Chiafari
authors.forename: Grantland
authors.initials: G
authors.lastname: Hillman
authors.forename: D Michele
authors.initials: DM
authors.lastname: Nikoloff
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007629:Kentucky / Q000453:epidemiology; D001523:Mental Disorders / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D015995:Prevalence; D011570:Psychiatry / Q000379:methods; D012196:Review Literature as Topic
chemical_list: D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6