title: Interethnic variability of CYP2D6 alleles and of predicted and measured metabolic phenotypes across world populations.
abstract: BACKGROUND
  The frequency of CYP2D6 alleles, related to either a lack of or increased enzymatic activity, which may lead to poor metabolism (PM) or ultrarapid metabolism (UM), can vary across ethnic groups and hence across geographic regions.
  
  
  METHODS
  Worldwide original research papers on CYP2D6 allelic frequencies, metabolic phenotype frequencies measured with a probe drug, and/or genotype frequencies that studied > 50 healthy volunteers, were included in analyses to describe the distributions of alleles, phenotypes predicted from genotypes (predicted poor metabolizers [gPMs], predicted ultrarapid metabolizers [gUMs]) and metabolic phenotypes (mPMs, mUMs) across ethnic groups and geographic regions. The analysis included 44,572 individuals studied in 172 original research papers.
  
  
  CONCLUSIONS
  As of today, Africa and Asia are under-represented in this area relative to the total number of their inhabitants, so that further studies in these regions are warranted. The CYP2D6*4 allele frequency was higher in Caucasians, CYP2D6*10 in East Asians, CYP2D6*41 and duplication/multiplication of active alleles in Middle Easterns, CYP2D6*17 in Black Africans and CYP2D6*29 in African Americans, than in other ethnic groups. Overall, gPMs and mPMs are more frequent among Caucasians, and gUMs among Middle Easterns and Ethiopians. However, mUMs could not be evaluated because only two studies were found presenting this information. Further studies including mUMs are thus warranted. There is a correspondence between gPMs and mPMs, but the few studies of mUMs meant that their relationship with gUMs could not be demonstrated. Finally, evolutionary aspects of the CYP2D6 allele distribution appear to support the Great Human Expansion model.
authors.affiliation: University of Extremadura Hospital, CICAB Clinical Research Center , Badajoz, 06080 , Spain allerena@unex.es.
authors.forename: Adrián
authors.initials: A
authors.lastname: LLerena
authors.forename: Maria Eugenia G
authors.initials: ME
authors.lastname: Naranjo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Rodrigues-Soares
authors.forename: Eva M
authors.initials: EM
authors.lastname: Penas-LLedó
authors.forename: Humberto
authors.initials: H
authors.lastname: Fariñas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona-Santos
mesh_terms: D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics*
chemical_list: D004364:Pharmaceutical Preparations; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; CYP2D6*10; CYP2D6*17; CYP2D6*29; CYP2D6*4; CYP2D6*41; ethnicity; poor metabolizers; population pharmacogenetics; ultrarapid metabolizers