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.
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.
Authors: T M Dodgen; C De J Labuschagne; A van Schalkwyk; F E Steffens; A Gaedigk; A D Cromarty; M Alessandrini; M S Pepper Journal: Pharmacogenomics J Date: 2015-10-27 Impact factor: 3.550
Authors: Carolina Céspedes-Garro; María-Eugenia G Naranjo; Fernanda Rodrigues-Soares; Adrián LLerena; Jorge Duconge; Lazara K Montané-Jaime; Hilda Roblejo; Humberto Fariñas; María de Los A Campos; Ronald Ramírez; Víctor Serrano; Carmen I Villagrán; Eva M Peñas-LLedó Journal: Pharmacogenomics Date: 2016-09-16 Impact factor: 2.533
Authors: M E G Naranjo; F de Andrés; A Delgado; J Cobaleda; E M Peñas-Lledó; A LLerena Journal: Pharmacogenomics J Date: 2016-06-07 Impact factor: 3.550
Authors: Jean C Dinh; Erin C Boone; Vincent S Staggs; Robin E Pearce; Wendy Y Wang; Roger Gaedigk; James Steven Leeder; Andrea Gaedigk Journal: Clin Pharmacol Ther Date: 2021-11-30 Impact factor: 6.875
Authors: Charity Nofziger; Amy J Turner; Katrin Sangkuhl; Michelle Whirl-Carrillo; José A G Agúndez; John L Black; Henry M Dunnenberger; Gualberto Ruano; Martin A Kennedy; Michael S Phillips; Houda Hachad; Teri E Klein; Andrea Gaedigk Journal: Clin Pharmacol Ther Date: 2019-12-09 Impact factor: 6.875
Authors: Andrea Gaedigk; Natalie Freeman; Toinette Hartshorne; Amanda K Riffel; David Irwin; Jeffrey R Bishop; Mark A Stein; Jeffrey H Newcorn; Lazara Karelia Montané Jaime; Mariana Cherner; J Steven Leeder Journal: Sci Rep Date: 2015-03-19 Impact factor: 4.379
Authors: Fernando de Andrés; Catalina Altamirano-Tinoco; Ronald Ramírez-Roa; Carlos F Montes-Mondragón; Pedro Dorado; Eva M Peñas-Lledó; Adrián LLerena Journal: Pharmacogenomics J Date: 2020-10-06 Impact factor: 3.550