title: CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure.
abstract: OBJECTIVE
  CYP2D6, a member of the cytochrome P450 superfamily, is responsible for the metabolism of about 25% of the commonly prescribed drugs. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of medication or therapeutic failure with recommended drug dosages. This study aimed to describe the CYP2D6 diversity at the global level.
  
  
  METHODS
  A total of 1060 individuals belonging to 52 worldwide-distributed populations were genotyped at 12 highly informative variable sites, as well as for gene deletion and duplications. Phenotypes were predicted on the basis of haplotype combinations.
  
  
  CONCLUSIONS
  Our study shows that (i) CYP2D6 diversity is far greater within than between populations and groups thereof, (ii) null or low-activity variants occur at high frequencies in various areas of the world, (iii) linkage disequilibrium is lowest in Africa and highest in the Americas. Patterns of variation, within and among populations, are similar to those observed for other autosomal markers (e.g. microsatellites and protein polymorphisms), suggesting that the diversity observed at the CYP2D6 locus reflects the same factors affecting variation at random genome markers.
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Finland. johanna.sistonen@helsinki.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Sistonen
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.forename: Guido
authors.initials: G
authors.lastname: Barbujani
authors.forename: Silvia
authors.initials: S
authors.lastname: Fuselli
mesh_terms: D000704:Analysis of Variance; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D016000:Cluster Analysis; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D005843:Geography; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D010641:Phenotype
chemical_list: D019389:Cytochrome P-450 CYP2D6