CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans

• Published in: The pharmacogenomics journal Vol. 12; no. 2; pp. 176 - 183
• Main Authors: LLerena, A, Dorado, P, Ramírez, R, González, I, Álvarez, M, Peñas-LLedó, E M, Pérez, B, Calzadilla, L R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2012; Nature Publishing Group
• Subjects: 631/1647/2217/457; 692/700/565/1436/434; Adolescent; Adult; Alleles; Biomedical and Life Sciences; Biomedicine; Cuba; CYP2D6 protein; Cytochrome P-450; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P450; Debrisoquin - metabolism; Environmental factors; Ethnic Groups - genetics; Female; Gene Expression; Gene frequency; Genetic variation; Genotype; Genotypes; Health aspects; Human Genetics; Humans; Hydroxylation; Male; Middle Aged; Nicaragua; Nicaraguans; Oncology; original-article; Pharmacotherapy; Phenotype; Phenotypes; Physiological aspects; Polymorphism, Genetic; Psychopharmacology; Young Adult; Cuba; Nicaragua; Spain; debrisoquine hydroxylation; phenotype; Latinos; CYP2D6; Cubans; Nicaraguans
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/tpj.2010.85

CYP2D6 genotype and debrisoquine metabolic ratio (MR) were analyzed in 133 Nicaraguan Mestizos (NMs) and 260 Cubans divided into Cuban Mestizos (CMs) and White Cubans (WCs). The frequencies of poor metabolizers (MR⩾12.6) were 6% in NMs, 3.9% in CMs and 5.3% in WCs. The frequencies of ultrarapid metabolizers (MR⩽0.1) were 0% in NMs, 2.3% in CMs and 5.3% in WCs. Mean (±s.d.) MR among extensive metabolizers (MR<12.6) was higher in NMs (1.5±1.6; n =118) than in CMs (1.0±1.3; n =124; P <0.001) and WCs (0.7±1.0; n =124; P <0.001). MR correlated with the ‘activity score’ of CYP2D6 genotypes ( P <0.05; r =−0.55). Mean MR was higher among NMs than WCs and CMs for groups classified as 1 ( P <0.05) or 2 ( P <0.01) ‘activity score’. In addition, mean (±s.d.) MR was higher among subjects carrying CYP2D6*17 than in CYP2D6 wt/wt ( P <0.001). The CYP2D6*10 allele was higher in NMs (3.1%) than in CMs (0.8%; P <0.05) and WCs (0.4%; P <0.05). CYP2D6*17 allele was higher in CMs (10.2%) than WC (2.7%; P <0.005) and NMs (0%). Thus, the variability in CYP2D6 phenotypes found may be related to differences in allele frequency among groups (that is, CYP2D6*10 and *17 highest in NMs and CMs, respectively). However, the influence of environmental factors or alleles different than those studied here cannot be ruled out.