Rodrigues Juliana Carla Gomes, Fernandes Marianne Rodrigues, Ribeiro-Dos-Santos André Maurício, de Araújo Gilderlanio Santana, de Souza Sandro José, Guerreiro João Farias, Ribeiro-Dos-Santos Ândrea, de Assumpção Paulo Pimentel, Santos Ney Pereira Carneiro Dos, Santos Sidney
Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belem 66073-000, Brazil.
Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belem 66075-110, Brazil.
J Pers Med. 2022 Jun 10;12(6):952. doi: 10.3390/jpm12060952.
Given the role of pharmacogenomics in the large variability observed in drug efficacy/safety, an assessment about the pharmacogenomic profile of patients prior to drug prescription or dose adjustment is paramount to improve adherence to treatment and prevent adverse drug reaction events. A population commonly underrepresented in pharmacogenomic studies is the Native American populations, which have a unique genetic profile due to a long process of geographic isolation and other genetic and evolutionary processes. Here, we describe the pharmacogenetic variability of Native American populations regarding 160 pharmacogenes involved in absorption, distribution, metabolism, and excretion processes and biological pathways of different therapies. Data were obtained through complete exome sequencing of individuals from 12 different Amerindian groups of the Brazilian Amazon. The study reports a total of 3311 variants; of this, 167 are exclusive to Amerindian populations, and 1183 are located in coding regions. Among these new variants, we found non-synonymous coding variants in the and the genes and variants with high allelic frequencies in intronic regions of the , and genes. Additionally, 332 variants with either high or moderate (disruptive or non-disruptive impact in protein effectiveness, respectively) significance were found with a minimum of 1% frequency in the Amazonian Amerindian population. The data reported here serve as scientific basis for future design of specific treatment protocols for Amazonian Amerindian populations as well as for populations admixed with them, such as the Northern Brazilian population.
鉴于药物基因组学在药物疗效/安全性所观察到的巨大变异性中所起的作用，在药物处方或剂量调整之前对患者的药物基因组概况进行评估对于提高治疗依从性和预防药物不良反应事件至关重要。在药物基因组学研究中通常代表性不足的人群是美洲原住民，由于长期的地理隔离以及其他遗传和进化过程，他们具有独特的遗传特征。在此，我们描述了美洲原住民人群在涉及不同疗法的吸收、分布、代谢、排泄过程以及生物途径的160个药物基因方面的药物遗传学变异性。数据是通过对来自巴西亚马逊地区12个不同美洲印第安人群体的个体进行全外显子测序获得的。该研究共报告了3311个变异；其中，167个是美洲印第安人群体所特有的，1183个位于编码区域。在这些新变异中，我们在 和 基因中发现了非同义编码变异，以及在 和 基因的内含子区域中具有高等位基因频率的变异。此外，在亚马逊美洲印第安人群体中发现了至少有1%频率的332个具有高或中等（分别对蛋白质有效性有破坏性或非破坏性影响）显著性的变异。这里报告的数据为未来为亚马逊美洲印第安人群体以及与他们混合的人群（如巴西北部人群）设计特定治疗方案提供了科学依据。
