Rodrigues-Soares Fernanda, Kehdy Fernanda S G, Sampaio-Coelho Julia, Andrade Poliana X C, Céspedes-Garro Carolina, Zolini Camila, Aquino Marla M, Barreto Mauricio L, Horta Bernardo L, Lima-Costa Maria Fernanda, Pereira Alexandre C, LLerena Adrián, Tarazona-Santos Eduardo
Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Gerência de Malária, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM, Brazil.
Pharmacogenomics J. 2018 Dec;18(6):749-759. doi: 10.1038/s41397-018-0015-7. Epub 2018 May 1.
We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity issues, being social constructs pervasively used in Brazilian society and medical studies; (2) are associated with disparities in access to health services, as well as in their representation in genetic studies, and (3), as we report here, explain a larger portion of the variance of pharmaco-allele frequencies than geography. We integrated a systematic review of studies on healthy volunteers (years 1968-2017) and the analysis of allele frequencies on three population-based cohorts from northeast, southeast, and south, the most populated regions of Brazil. Cross-validation of results from these both approaches suggest that, despite methodological heterogeneity of the 120 studies conducted on 51,747 healthy volunteers, allele frequencies estimates from systematic review are reliable. We report differences in allele frequencies between color categories that persist despite the homogenizing effect of >500 years of admixture. Among clinically relevant variants: CYP2C92 (null), CYP3A53 (defective), SLCO1B1-rs4149056(C), and VKORC1-rs9923231(A) are more frequent in Whites than in Blacks. Brazilian Native Americans show lower frequencies of CYP2C92, CYP2C1917 (increased activity), and higher of SLCO1B1-rs4149056(C) than other Brazilian populations. We present the most current and informative database of pharmaco-allele frequencies in Brazilian healthy volunteers.
我们展示了在巴西研究的39种药物遗传学生物标志物的等位基因频率，以及它们在自我报告的种族/肤色类别中的分布情况，这些类别：（1）涉及对血统、形态特征以及文化/身份问题的多种认知，是巴西社会和医学研究中普遍使用的社会建构；（2）与获得医疗服务的差异以及在基因研究中的代表性相关；（3）正如我们在此报告的，比地理位置解释了更大比例的药物等位基因频率方差。我们整合了对健康志愿者研究（1968 - 2017年）的系统综述，以及对来自巴西人口最多的东北部、东南部和南部三个基于人群的队列的等位基因频率分析。这两种方法结果的交叉验证表明，尽管对51,747名健康志愿者进行的120项研究存在方法学异质性，但系统综述得出的等位基因频率估计是可靠的。我们报告了尽管经过500多年的混合有同质化效应，但肤色类别之间的等位基因频率差异仍然存在。在临床相关变体中：CYP2C92（无效）、CYP3A53（缺陷）、SLCO1B1 - rs4149056（C）和VKORC1 - rs9923231（A）在白人中的频率高于黑人。巴西原住民中CYP2C92、CYP2C1917（活性增加）的频率低于其他巴西人群，而SLCO1B1 - rs4149056（C）的频率则更高。我们展示了巴西健康志愿者中最新且信息丰富的药物等位基因频率数据库。
