CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

<p>Abstract</p> <p>Background</p> <p>Recent studies have reported the clinical importance of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.</p> <p>Methods</p> <p>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 <it>ABCB1</it>c.C3435T (rs1045642), <it>CYP2C19*2 </it>(rs4244285), <it>CYP2C19*3 </it>(rs4986893), <it>CYP2C19*4 </it>(rs28399504), <it>CYP2C19*5 </it>(rs56337013), and <it>CYP2C19*17 </it>(rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The <it>CYP2C19*3</it>, <it>CYP2C19*4 </it>and <it>CYP2C19*5 </it>variants were genotyped in a subsample of subjects (300 samples randomly selected).</p> <p>Results</p> <p>The <it>CYP2C19*3 </it>and <it>CYP2C19*5 </it>variant alleles were not detected and the <it>CYP2C19*4 </it>variant allele presented a frequency of 0.3%. The allelic frequencies for the <it>ABCB1</it>c.C3435T, <it>CYP2C19*2 </it>and <it>CYP2C19*17 </it>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.</p> <p>Conclusion</p> <p>Our findings indicate the existence of inter-ethnic differences in the <it>ABCB1 </it>and <it>CYP2C19 </it>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.</p

<it>SLCO1B1 </it>rs4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population: Amerindians as a high risk ethnic group

Abstract Background Recent studies reported the association between SLCO1B1 polymorphisms and the development of statin-induced myopathy. In the scenario of the Brazilian population, being one of the most heterogeneous in the world, the main aim here was to evaluate SLCO1B1 polymorphisms according to ethnic groups as an initial step for future pharmacogenetic studies. Methods One hundred and eighty-two Amerindians plus 1,032 subjects from the general urban population were included. Genotypes for the SLCO1B1 rs4149056 (c.T521C, p.V174A, exon 5) and SLCO1B1 rs4363657 (g.T89595C, intron 11) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis with the Rotor Gene 6000® instrument. Results The frequencies of the SLCO1B1 rs4149056 and rs4363657 C variant allele were higher in Amerindians (28.3% and 26.1%) and were lower in African descent subjects (5.7% and 10.8%) compared with Mulatto (14.9% and 18.2%) and Caucasian descent (14.8% and 15.4%) ethnic groups (p Conclusion Our findings indicate interethnic differences for the SLCO1B1 rs4149056 C risk allele frequency among Brazilians. These data will be useful in the development of effective programs for stratifying individuals regarding adherence, efficacy and choice of statin-type.</p