title: Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population.
abstract: OBJECTIVE
  The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to the metabolism of about 30% of all drugs. For analysis of the ethnic-related differences in drug disposition and as a preparation for routine genotyping, we examined CYP2C19 and CYP2D6 mutations in a large Turkish population.
  
  
  METHODS
  CYP2C19 and CYP2D6 alleles were determined with use of genomic deoxyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays.
  
  
  RESULTS
  From 404 subjects genotyped for CYP2C19, allele frequencies of CYP2C19*1 (wt), CYP2C19*2 (ml), and CYP2C19*3 (m2) were 0.88, 0.12, and 0.004, respectively; mutations m3 and m4 were not found. Four individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly lower frequency compared to Middle European populations. Among 404 subjects genotyped for CYP2D6, most frequent alleles were CYP2D6*1 (allele frequency 0.37), *2 (0.35), *4 (0.11), *10 (0.06), duplications *1x2, *2x2, or *4x2 (0.06), *5 (0.01), and *17(0.01). Overall, six subjects (1.49%) were predicted to be CYP2D6 poor metabolizers, and 35 subjects (8.66%) were predicted to be ultrarapid metabolizers as a result of CYP2D6 gene duplications.
  
  
  CONCLUSIONS
  Obviously, within Europe there is a north-south gradient, with decreasing frequency of poor metabolizers of CYP2C19 and CYP2D6 to the south and a corresponding increase of ultrarapid metabolizers of CYP2D6. As in other white groups, only CYP2C19*2 plays a relevant role for the CYP2C19 poor metabolizer phenotype. The mutational spectrum of CYP2D6 indicated partial ethnic relationships to Asian and African populations.
authors.affiliation: Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University, Berlin, Germany.
authors.forename: A S
authors.initials: AS
authors.lastname: Aynacioglu
authors.forename: C
authors.initials: C
authors.lastname: Sachse
authors.forename: A
authors.initials: A
authors.lastname: Bozkurt
authors.forename: S
authors.initials: S
authors.lastname: Kortunay
authors.forename: M
authors.initials: M
authors.lastname: Nacak
authors.forename: T
authors.initials: T
authors.lastname: Schröder
authors.forename: S O
authors.initials: SO
authors.lastname: Kayaalp
authors.forename: I
authors.initials: I
authors.lastname: Roots
authors.forename: J
authors.initials: J
authors.lastname: Brockmöller
mesh_terms: D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005060:Europe; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014421:Turkey; D044465:White People / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6