BACKGROUND: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. METHODS: One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). RESULTS: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. CONCLUSION: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.
BACKGROUND: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. METHODS: One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). RESULTS: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. CONCLUSION: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.
Authors: Nita A Limdi; Mia Wadelius; Larisa Cavallari; Niclas Eriksson; Dana C Crawford; Ming-Ta M Lee; Chien-Hsiun Chen; Alison Motsinger-Reif; Hersh Sagreiya; Nianjun Liu; Alan H B Wu; Brian F Gage; Andrea Jorgensen; Munir Pirmohamed; Jae-Gook Shin; Guilherme Suarez-Kurtz; Stephen E Kimmel; Julie A Johnson; Teri E Klein; Michael J Wagner Journal: Blood Date: 2010-03-04 Impact factor: 22.113
Authors: M M Ameyaw; F Regateiro; T Li; X Liu; M Tariq; A Mobarek; N Thornton; G O Folayan; J Githang'a; A Indalo; D Ofori-Adjei; D A Price-Evans; H L McLeod Journal: Pharmacogenetics Date: 2001-04
Authors: Rafael O Alvim; Silvia R S Freitas; Noely E Ferreira; Paulo C J L Santos; Roberto S Cunha; José G Mill; José E Krieger; Alexandre C Pereira Journal: Lipids Health Dis Date: 2010-11-08 Impact factor: 3.876
Authors: S Hoffmeyer; O Burk; O von Richter; H P Arnold; J Brockmöller; A Johne; I Cascorbi; T Gerloff; I Roots; M Eichelbaum; U Brinkmann Journal: Proc Natl Acad Sci U S A Date: 2000-03-28 Impact factor: 11.205
Authors: I Fricke-Galindo; C Céspedes-Garro; F Rodrigues-Soares; M E G Naranjo; Á Delgado; F de Andrés; M López-López; E Peñas-Lledó; A LLerena Journal: Pharmacogenomics J Date: 2015-10-27 Impact factor: 3.550
Authors: Paulo Caleb Junior Lima Santos; Ana Carolina Moron Gagliardi; Márcio Hiroshi Miname; Ana Paula Chacra; Raul Dias Santos; Jose Eduardo Krieger; Alexandre Costa Pereira Journal: Eur J Clin Pharmacol Date: 2011-09-18 Impact factor: 2.953
Authors: Alma Faviola Favela-Mendoza; Gabriela Martinez-Cortes; Marcelo Hernandez-Zaragoza; Joel Salazar-Flores; Jose Francisco Muñoz-Valle; Victor Manuel Martinez-Sevilla; Noemi Yolanda Velazquez-Suarez; Hector Rangel-Villalobos Journal: J Genet Date: 2015-03 Impact factor: 1.166
Authors: Letícia C Tavares; Nubia E Duarte; Leiliane R Marcatto; Renata A G Soares; Jose E Krieger; Alexandre C Pereira; Paulo Caleb Junior Lima Santos Journal: Eur J Clin Pharmacol Date: 2018-07-26 Impact factor: 2.953
Authors: Gilberto Vargas-Alarcón; Julián Ramírez-Bello; Aurora de la Peña; Beatriz Calderón-Cruz; Marco Antonio Peña-Duque; Marco Antonio Martínez-Ríos; Silvestre Ramírez-Fuentes; Oscar Pérez-Méndez; José Manuel Fragoso Journal: Mol Biol Rep Date: 2014-08-09 Impact factor: 2.316