Arrifano Gabriela P F, Martín-Doimeadios Rosa C R, Jiménez-Moreno María, Fernández-Trujillo Sergio, Augusto-Oliveira Marcus, Souza-Monteiro José R, Macchi Barbarella M, Alvarez-Leite Jacqueline I, do Nascimento José L M, Amador Marcos T, Santos Sidney, Ribeiro-Dos-Santos Ândrea, Silva-Pereira Liz C, Oriá Reinaldo B, Crespo-Lopez Maria E
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
Department of Analytical Chemistry and Food Technology, Faculty of Environmental Sciences and Biochemistry, University of Castilla-La Mancha, Toledo, Spain.
Front Genet. 2018 Jul 27;9:285. doi: 10.3389/fgene.2018.00285. eCollection 2018.
Human exposure to mercury is a serious problem of public health in Amazon. As in other vulnerable populations throughout the world, Amazonian riverine populations are chronically exposed to this metal and some symptoms of mercury intoxication were already detected in these populations. However, studies on the genetic susceptibility to mercury toxicity in the Amazon are scarce, and they tested a limited number of individuals. In this context, apolipoprotein E gene () is a key element with a well-established association among their alleles and the neurodegenerative consequences of mercury intoxication. However, no studies have addressed genotyping in Amazonian exposed populations. Additionally, epidemiological studies with genotyping in Amazon have been restricted to indigenous populations. Therefore, this work analyzed for the first time the genotypic and allelic profiles of in Amazonian riverine populations chronically exposed to mercury. Eight hundred and twenty three individuals were enrolled in our study donating blood (794) and/or hair (757). genotyping was analyzed by real-time PCR. Total mercury and mercury species were quantified by ICP-MS and GC-pyro-AFS, respectively. Genomic ancestry markers were evaluated by multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. The 𝜀3 and 𝜀3/𝜀3 were the most frequent allele and genotype, respectively, followed by 𝜀4 allele and 𝜀3/𝜀4 genotype. Only 𝜀2/𝜀2 genotype was not found, suggesting that the absence of this genotype is a generalized phenomenon in Amazon. Also, our data supported an association between the presence of and the Amerindian origin in these populations. Fifty-nine individuals were identified at maximum risk with levels of mercury above 10 μg/g and the presence of . Interestingly, among individuals with high mercury content, -carriers had high mercury levels than -carriers, pointing to a different heavy metal accumulation according to the allele. These data suggest that , in addition to a possible pharmacodynamic effect, may influence pharmacokinetically the mercury exposure causing its higher accumulation and leading to worse deleterious consequences. Our results may aid in the development of prevention strategies and health policy decision-making regarding these at-risk vulnerable populations.
人类接触汞是亚马逊地区一个严重的公共卫生问题。与世界其他脆弱人群一样，亚马逊河流域居民长期接触这种金属，并且在这些人群中已经检测到汞中毒的一些症状。然而，关于亚马逊地区汞毒性遗传易感性的研究很少，而且所测试的个体数量有限。在这种情况下，载脂蛋白E基因（）是一个关键因素，其等位基因与汞中毒的神经退行性后果之间存在明确的关联。然而，尚未有研究对亚马逊地区接触汞的人群进行基因分型。此外，亚马逊地区进行基因分型的流行病学研究仅限于土著人群。因此，这项工作首次分析了长期接触汞的亚马逊河流域居民的基因和等位基因谱。我们的研究招募了823名个体，他们捐献了血液（794份）和/或头发（757份）。通过实时PCR分析基因分型。分别通过电感耦合等离子体质谱法（ICP-MS）和气相色谱-热解原子荧光光谱法（GC-pyro-AFS）对总汞和汞形态进行定量。通过多重PCR反应评估基因组祖先标记，在ABI 3130遗传分析仪上通过毛细管电泳分离，并在GeneMapper ID v3.2上进行分析。ε3和ε3/ε3分别是最常见的等位基因和基因型，其次是ε4等位基因和ε3/ε4基因型。仅未发现ε2/ε2基因型，这表明该基因型的缺失在亚马逊地区是一种普遍现象。此外，我们的数据支持了在这些人群中基因的存在与美洲印第安人起源之间的关联。确定了59名汞含量高于10μg/g且存在该基因的个体处于最高风险。有趣的是，在汞含量高的个体中，携带该基因的个体汞水平高于非携带者，这表明根据等位基因不同，重金属积累情况也不同。这些数据表明，该基因除了可能具有药效学作用外，还可能在药代动力学上影响汞暴露，导致其更高的积累并产生更严重的有害后果。我们的结果可能有助于制定针对这些高危脆弱人群的预防策略和卫生政策决策。
