Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure
Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure
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DOI：
10.1016/j.envpol.2016.10.058
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发表时间：
2017-02-01
影响因子：
8.9
通讯作者：
Al-Ghadeer, Abdul Rahman M.
中科院分区：
文献类型：
--
作者：
Korashy, Hesham M.;Attafi, Ibraheem M.;Al-Ghadeer, Abdul Rahman M.
重金属是最常见的有毒物质，长期接触会增加对各种疾病的易感性。我们之前的研究表明，生活在矿区附近的健康志愿者受到重金属的严重污染，与一些解毒基因、外源代谢酶和DNA修复基因的表达发生显著变化有关。然而，大多数与疾病相关的分子靶基因的改变仍然是未知的。因此，本研究的目的是(a)评估基因表达谱，(b)使用微阵列分析确定与矿区长期暴露于环境重金属相关的毒性和潜在相关的人类疾病结果。为此，研究人员将40名来自重金属污染地区（沙特阿拉伯Mahd Al-Dhahab市）的健康男性志愿者和20名来自非重金属污染地区的健康男性志愿者纳入研究。采用PAXgene blood RNA管从全血中分离总RNA，利用Affymetrix U219基因芯片进行反转录和杂交。基因芯片分析结果显示，共鉴定出2129个基因存在差异表达，其中共有425个基因在重金属暴露组中存在差异表达。匠心途径分析显示，重金属暴露组中基因改变最多的疾病包括血液学和发育障碍，主要是肾脏和泌尿系统疾病。定量实时聚合酶链反应与微阵列数据密切匹配。重要的是，基因相关疾病的变化归因于编码蛋白质合成的基因的改变。肾脏和泌尿系统疾病是与重金属暴露组最常见的疾病。因此，需要进一步的研究来验证这些基因，这些基因可以作为早期生物标志物来预防肾损伤。(C) 2016 Elsevier Ltd.版权所有。
Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these genes, which could be used as early biomarkers to prevent renal injury. (C) 2016 Elsevier Ltd. All rights reserved.