Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, (Av, Dr, Enéas de Carvalho Aguiar, 44), Sao Paulo, (05403-000), Brazil.
BMC Med Genet. 2011 Oct 12;12:136. doi: 10.1186/1471-2350-12-136.
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.
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.
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<0.001 and p<0.001, respectively). Linkage disequilibrium analysis show that these variant alleles are in different linkage disequilibrium patterns depending on the ethnic origin.
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.
最近的研究报告称 SLCO1B1 多态性与他汀类药物诱导的肌病的发展有关。在巴西这个世界上最多样化的人群中,主要目的是根据种族群体评估 SLCO1B1 多态性,作为未来药物遗传学研究的初步步骤。
共纳入 182 名美洲印第安人和 1032 名城市普通人群。采用聚合酶链反应(PCR)结合高分辨率熔解曲线分析(HRM)技术检测 SLCO1B1 rs4149056(c.T521C,p.V174A,外显子 5)和 SLCO1B1 rs4363657(g.T89595C,内含子 11)多态性。
与黑白混血儿(14.9%和 18.2%)和白种人(14.8%和 15.4%)相比,美洲印第安人(28.3%和 26.1%)中 SLCO1B1 rs4149056 和 rs4363657 C 变体等位基因的频率更高,而非洲裔受试者(5.7%和 10.8%)的频率更低(p<0.001 和 p<0.001)。连锁不平衡分析表明,这些变体等位基因根据种族起源呈现不同的连锁不平衡模式。
我们的研究结果表明,巴西不同种族之间 SLCO1B1 rs4149056 C 风险等位基因频率存在种族差异。这些数据将有助于制定有效的个体化分层方案,以提高患者的依从性、疗效和他汀类药物的选择。