title: Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants.
abstract: BACKGROUND
  The highly polymorphic CYP2D6 gene has extensively been studied in many populations, but there is a void of knowledge regarding CYP2D6 pharmacogenetics and activity in populations with unique ancestries and admixture, such as those residing in Trinidad and Tobago.
  
  
  METHODS
  167 healthy Indo- and 103 Afro-Trinidadians were phenotyped with dextromethorphan and extensively genotyped. Gene resequencing was performed to resolve cases with genotype/phenotype discordance.
  
  
  RESULTS
  CYP2D6 activity did not differ between the Indo-Trinidadians and Afro-Trinidadians. Poor metabolizers were, however, more frequent in the Indo-Trinidadians (4.19 vs 1.94%), and unique allele frequency patterns were observed. Two novel nonfunctional allelic variants were found among the Indo-Trinidadians in two discordant cases. CYP2D6*100 is characterized by a single nucleotide deletion and CYP2D6*101 by a 19-bp deletion; both cause frameshifts.
  
  
  CONCLUSIONS
  Our study underscores the importance of thoroughly characterizing the genetic make up of unique populations when considering pharmacogenetic testing for individualized therapy.
authors: Pharmacology Unit, Department of Paraclinical Sciences, Faculty of Medical Sciences, The University of The West Indies, St Augustine, Trinidad & Tobago. lazara.montane@sta.uwi.edu
authors: Lazara Karelia
authors: LK
authors: Montané Jaime
authors: Anthony
authors: A
authors: Lalla
authors: Werner
authors: W
authors: Steimer
authors: Andrea
authors: A
authors: Gaedigk
mesh_terms: D000328:Adult; D044383:Black People; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014300:Trinidad and Tobago
chemical_list: D019389:Cytochrome P-450 CYP2D6