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Pharmacogenomics. 2013 Feb;14(3):261-76. doi: 10.2217/pgs.12.207.

Characterization of the CYP2D6 gene locus and metabolic activity in Indo- and Afro-Trinidadians: discovery of novel allelic variants.

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1
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

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.

MATERIALS & 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.

CONCLUSION:

Our study underscores the importance of thoroughly characterizing the genetic make up of unique populations when considering pharmacogenetic testing for individualized therapy.

PMID:
23394389
DOI:
10.2217/pgs.12.207
[Indexed for MEDLINE]
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