title: CYP2D6 -1584C>G promoter polymorphism and debrisoquine ultrarapid hydroxylation in healthy volunteers.
abstract: OBJECTIVE
  The CYP2D6 -1584C>G polymorphism (rs1080985) has been identified as a major factor for CYP2D6 expression and function, with the mutant -1584G promoter type being consistently associated with significantly greater expression than -1584C. It may therefore be associated with ultrarapid metabolism. The objective of the present study was to explore the relationship between the CYP2D6 -1584C>G polymorphism and the debrisoquine metabolic ratio in healthy volunteers in order to evaluate its potential impact on the ultrarapid CYP2D6 hydroxylation capacity.
  
  
  METHODS
  The CYP2D6 -1584C>G polymorphism was analyzed in 320 unrelated healthy individuals who were previously phenotyped for debrisoquine hydroxylation.
  
  
  RESULTS
  The metabolic ratio (log10 mean ± standard deviation) of individuals with the -1584G allele was lower than that of individuals with the -1584C allele for carriers of one active CYP2D6 gene (-0.13 ± 0.33 and 0.17 ± 0.52, respectively; p < 0.05) or two active CYP2D6 genes (-0.32 ± 0.39 and -0.20 ± 0.44, respectively; p < 0.05).
  
  
  CONCLUSIONS
  The presence of the -1584G allele in the promoter region of the CYP2D6 gene was related to a high CYP2D6 hydroxylation capacity.
authors.affiliation: CICAB Clinical Research Centre, Extremadura University Hospital & Medical School, Badajoz 06080, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Llerena
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Ronald
authors.initials: R
authors.lastname: Ramírez
authors.forename: Luis R
authors.initials: LR
authors.lastname: Calzadilla
authors.forename: Eva
authors.initials: E
authors.lastname: Peñas-Lledó
authors.forename: Mayra
authors.initials: M
authors.lastname: Álvarez
authors.forename: María E G
authors.initials: ME
authors.lastname: Naranjo
authors.forename: Idilio
authors.initials: I
authors.lastname: González
authors.forename: Bárbaro
authors.initials: B
authors.lastname: Pérez
mesh_terms: D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003647:Debrisoquin / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D064368:Healthy Volunteers; D006579:Heterozygote; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin